Clinical characteristics and outcomes in elderly patients undergoing transsphenoidal surgery for nonfunctioning pituitary adenoma.

OBJECTIVE: Life expectancy has increased over the past century, causing a shift in the demographic distribution toward older age groups. Elderly patients comprise up to 14% of all patients with pituitary tumors, with most lesions being nonfunctioning pituitary adenomas (NFPAs). Here, the authors evaluated demographics, outcomes, and postoperative complications between nonelderly adult and elderly NFPA patients. METHODS: A retrospective review of 908 patients undergoing transsphenoidal surgery (TSS) for NFPA at a single institution from 2007 to 2019 was conducted. Clinical and surgical outcomes and postoperative complications were compared between nonelderly adult (age ≥ 18 and ≤ 65 years) and elderly patients (age > 65 years). RESULTS: There were 614 and 294 patients in the nonelderly and elderly groups, respectively. Both groups were similar in sex (57.3% vs 60.5% males; p = 0.4), tumor size (2.56 vs 2.46 cm; p = 0.2), and cavernous sinus invasion (35.8% vs 33.7%; p = 0.6). Regarding postoperative outcomes, length of stay (1 vs 2 days; p = 0.5), extent of resection (59.8% vs 64.8% gross-total resection; p = 0.2), CSF leak requiring surgical revision (4.3% vs 1.4%; p = 0.06), 30-day readmission (8.1% vs 7.3%; p = 0.7), infection (3.1% vs 2.0%; p = 0.5), and new hypopituitarism (13.9% vs 12.0%; p = 0.3) were similar between both groups. Elderly patients were less likely to receive adjuvant radiation (8.7% vs 16.3%; p = 0.009), undergo future reoperation (3.8% vs 9.5%; p = 0.003), and experience postoperative diabetes insipidus (DI) (3.7% vs 9.4%; p = 0.002), and more likely to have postoperative hyponatremia (26.7% vs 16.4%; p < 0.001) and new cranial nerve deficit (1.9% vs 0.0%; p = 0.01). Subanalysis of elderly patients showed that patients with higher Charlson Comorbidity Index scores had comparable outcomes other than higher DI rates (8.1% vs 0.0%; p = 0.006). Elderly patients' postoperative sodium peaked and troughed on postoperative day 3 (POD3) (mean 138.7 mEq/L) and POD9 (mean 130.8 mEq/L), respectively, compared with nonelderly patients (peak POD2: mean 139.9 mEq/L; trough POD8: mean 131.3 mEq/L). CONCLUSIONS: The authors' analysis revealed that TSS for NFPA in elderly patients is safe with low complication rates. In this cohort, more elderly patients experienced postoperative hyponatremia, while more nonelderly patients experienced postoperative DI. These findings, combined with the observation of higher DI in patients with more comorbidities and elderly patients experiencing later peaks and troughs in serum sodium, suggest age-related differences in sodium regulation after NFPA resection. The authors hope that their results will help guide discussions with elderly patients regarding risks and outcomes of TSS.

Machine learning-based prediction of outcomes of the endoscopic endonasal approach in Cushing disease: is the future coming?

OBJECTIVE: Machine learning (ML) is an innovative method to analyze large and complex data sets. The aim of this study was to evaluate the use of ML to identify predictors of early postsurgical and long-term outcomes in patients treated for Cushing disease (CD). METHODS: All consecutive patients in our center who underwent surgery for CD through the endoscopic endonasal approach were retrospectively reviewed. Study endpoints were gross-tumor removal (GTR), postsurgical remission, and long-term control of disease. Several demographic, radiological, and histological factors were assessed as potential predictors. For ML-based modeling, data were randomly divided into 2 sets with an 80% to 20% ratio for bootstrapped training and testing, respectively. Several algorithms were tested and tuned for the area under the curve (AUC). RESULTS: The study included 151 patients. GTR was achieved in 137 patients (91%), and postsurgical hypersecretion remission was achieved in 133 patients (88%). At last follow-up, 116 patients (77%) were still in remission after surgery and in 21 patients (14%), CD was controlled with complementary treatment (overall, of 131 cases, 87% were under control at follow-up). At internal validation, the endpoints were predicted with AUCs of 0.81-1.00, accuracy of 81%-100%, and Brier scores of 0.035-0.151. Tumor size and invasiveness and histological confirmation of adrenocorticotropic hormone (ACTH)-secreting cells were the main predictors for the 3 endpoints of interest. CONCLUSIONS: ML algorithms were used to train and internally validate robust models for all the endpoints, giving accurate outcome predictions in CD cases. This analytical method seems promising for potentially improving future patient care and counseling; however, careful clinical interpretation of the results remains necessary before any clinical adoption of ML. Moreover, further studies and increased sample sizes are definitely required before the widespread adoption of ML to the study of CD.

Pretemporal trans-Meckel's cave transtentorial approach for large petroclival meningiomas.

OBJECTIVE Despite the advances in skull base techniques, large petroclival meningiomas (PCMs) still pose a challenge to neurosurgeons. The authors' objective of this study was to describe a pretemporal trans-Meckel's cave transtentorial approach for large PCMs and to report the surgical outcomes. METHODS From 2014 to 2017, patients harboring large PCMs (> 3 cm) and undergoing their first resection via this procedure at the authors' institute were included. In combination with pretemporal transcavernous and anterior transpetrosal approaches, the trans-Meckel's cave transtentorial route was created. Surgical details are described and a video demonstrating the procedure is included. Retrospective review of the medical records and imaging studies was performed. RESULTS A total of 18 patients (6 men and 12 women) were included in this study, with mean age of 53 years. The mean sizes of the preoperative and postoperative PCMs were 4.36 cm × 4.09 cm × 4.13 cm (length × width × height) and 0.83 cm × 1.08 cm × 0.75 cm, respectively. Gross-total removal was performed in 7 patients, near-total removal (> 95%) in 7 patients, and subtotal removal in 4 patients (> 90% in 3 patients and > 85% in 1 patient). There were no surgical deaths or patients with postoperative hemiplegia. Surgical complications included transient cranial nerve (CN) III palsy (all patients, resolved in 3 months), transient CN VI palsy (2 patients), CN IV palsy (3 patients, partial recovery), hydrocephalus (3 patients), and CSF otorrhea (1 patient). Temporal lobe retraction-related neurological deficits were not observed. CONCLUSIONS A pretemporal trans-Meckel's cave transtentorial approach offers large surgical exposure and multiple trajectories to the suprasellar, interpeduncular, prepontine, and upper-half clival regions without overt traction, which is mandatory to remove large PCMs. To unlock Meckel's cave where a large PCM lies abutting the cave, pretemporal transcavernous and anterior transpetrosal approaches are prerequisites to create adequate exposure for the final trans-Meckel's cave step.

Safe maximal resection of primary cavernous sinus meningiomas via a minimal anterior and posterior combined transpetrosal approach.

OBJECTIVE Meningiomas arising from the cavernous sinus (CS) continue to be a significant technical challenge, and resection continues to carry a relatively higher risk of neurological morbidity in patients with these lesions because of the tumor's proximity to neurovascular structures. The authors report the surgical outcomes of 9 patients with primary CS meningiomas (CSMs) that were surgically treated using a minimal anterior and posterior combined (MAPC) transpetrosal approach, and they emphasize the usefulness of the approach. METHODS This retrospective study included 9 patients who underwent surgery for CSM treatment between 2015 and 2016 via the MAPC transpetrosal approach. Two patients were men and 7 were women, with a mean age of 58.5 years (39-72 years). Five patients (55.5%) had undergone previous treatment. The surgical technique consisted of a temporo-occipito-suboccipital craniotomy and exposure of the posterolateral part of the CS via the presigmoidal MAPC approach. After opening Meckel's cave and identifying the 3rd-5th cranial nerves in the prepontine cistern, Parkinson's triangle and supratrochlear triangles were opened. Finally, the tumor occupying the posterolateral part of the CS was removed. RESULTS All lesions were safely and maximally removed, with preservation of external ocular movements and preoperative Karnofsky Performance Scale scores. The mean extent of resection was 77.0% (range 58.7%-95.4%). Six patients underwent adjuvant therapy in the form of stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) during the follow-up period; none of these patients experienced recurrence. CONCLUSION The authors conclude that the MAPC transpetrosal approach could be superior to other approaches for CSMs, as it provides direct visual access to the posterolateral portion of the CS. In their experience, this approach is an alternative and better option for safe maximal resection of CSMs.

Surgical management of giant sphenoid wing meningiomas encasing major cerebral arteries.

OBJECTIVE Sphenoid wing meningiomas are a heterogeneous group of tumors with variable surgical risks and prognosis. Those that have grown to a very large size, encasing the major cerebral arteries, are associated with a high risk of stroke. In reviewing the authors' series of giant sphenoid wing meningiomas, the goal was to evaluate how the extent of the tumor's invasion of surrounding structures affected the ability to safely remove the tumor and restore function. METHODS The authors conducted a retrospective study of a series of giant sphenoid wing meningiomas operated on between 1996 and 2016. Inclusion criteria were meningiomas with a globoid component ≥ 6 cm, encasing at least 1 major intradural cerebral artery. Extent of resection was measured according to Simpson grade. RESULTS This series included 12 patients, with a mean age of 59 years. Visual symptoms were the most common clinical presentation. There was complete or partial encasement of all 3 major cerebral arteries except for 3 cases in which only the anterior cerebral artery was not involved. The lateral wall of the cavernous sinus was invaded in 8 cases (67%) and the optic canal in 6 (50%). Complete resection was achieved in 2 cases (Simpson grades 2 and 3). In the remaining 10 cases of partial resection (Simpson grade 4), radical removal (> 90%) was achieved in 7 cases (70%). In the immediate postoperative period, there were no deaths. Four of 9 patients with visual deficits improved, while the 5 others remained unchanged. Two patients experienced transient neurological deficits. Other than an asymptomatic lacuna of the internal capsule, there were no ischemic lesions following surgery. Tumor recurrence occurred in 5 patients, between 24 and 168 months (mean 61 months) following surgery. CONCLUSIONS Although these giant lesions encasing major cerebral arteries are particularly treacherous for surgery, this series demonstrates that it is possible to safely achieve radical removal and at times even gross-total resection. However, the risk of recurrence remains high and larger studies are needed to see if and how improvement can be achieved, whether in surgical technique or technological advances, and by determining the timing and modality of adjuvant radiation therapy.

Endoscopic transorbital and endonasal approach for trigeminal schwannomas: a retrospective multicenter analysis (KOSEN-005).

OBJECTIVE: Trigeminal schwannomas are rare neoplasms with an incidence of less than 1% that require a comprehensive surgical strategy. These tumors can occur anywhere along the path of the trigeminal nerve, capable of extending intradurally into the middle and posterior fossae, and extracranially into the orbital, pterygopalatine, and infratemporal fossa. Recent advancements in endoscopic surgery have suggested a more minimally invasive and direct route for tumors in and around Meckel's cave, including the endoscopic endonasal approach (EEA) and endoscopic transorbital superior eyelid approach (ETOA). The authors assess the feasibility and outcomes of EEA and ETOA for trigeminal schwannomas. METHODS: A retrospective multicenter analysis was performed on 25 patients who underwent endoscopic surgical treatment for trigeminal schwannomas between September 2011 and February 2019. Thirteen patients (52%) underwent EEA and 12 (48%) had ETOA, one of whom underwent a combined approach with retrosigmoid craniotomy. The extent of resection, clinical outcome, and surgical morbidity were analyzed to evaluate the feasibility and selection of surgical approach between EEA and ETOA based on predominant location of trigeminal schwannomas. RESULTS: According to predominant tumor location, 9 patients (36%) had middle fossa tumors (Samii type A), 8 patients (32%) had dumbbell-shaped tumors located in the middle and posterior cranial fossae (Samii type C), and another 8 patients (32%) had extracranial tumors (Samii type D). Gross-total resection (GTR, n = 12) and near-total resection (NTR, n = 7) were achieved in 19 patients (76%). The GTR/NTR rates were 81.8% for ETOA and 69.2% for EEA. The GTR/NTR rates of ETOA and EEA according to the classifications were 100% and 50% for tumors confined to the middle cranial fossa, 75% and 33% for dumbbell-shaped tumors located in the middle and posterior cranial fossae, and 50% and 100% for extracranial tumors. There were no postoperative CSF leaks. The most common preoperative symptom was trigeminal sensory dysfunction, which improved in 15 of 21 patients (71.4%). Three patients experienced new postoperative complications such as vasospasm (n = 1), wound infection (n = 1), and medial gaze palsy (n = 1). CONCLUSIONS: ETOA provides adequate access and resectability for trigeminal schwannomas limited in the middle fossa or dumbbell-shaped tumors located in the middle and posterior fossae, as does EEA for extracranial tumors. Tumors predominantly involving the posterior fossa still remain a challenge in endoscopic surgery.

Sphenoorbital meningioma: a unique skull base tumor. Surgical technique and results.

OBJECTIVE: Sphenoorbital meningioma (SOM) is a unique skull base tumor, characterized by infiltrative involvement and hyperostosis primarily of the lesser wing of sphenoid bone, with frequent involvement of the orbital compartment. SOM often manifests with proptosis and visual impairment. Surgical technique and outcome are highly variable among studies reported in the literature. The authors present a single-surgeon experience with SOM. METHODS: A retrospective review of a prospectively maintained institutional database was performed. A blinded imaging review by 2 study team members was completed to confirm SOM, after which chart review was carried out to capture demographics and outcomes. All statistical testing was completed using JMP Pro version 14.1.0, with significance defined as p < 0.05. RESULTS: Forty-seven patients who underwent surgery between 2000 and 2017 were included. The median age at surgery was 47 years (range 36-70 years), 81% of patients were female, and the median follow-up was 43 months (range 0-175 months). All operations were performed via a frontotemporal craniotomy, orbitooptic osteotomy, and anterior clinoidectomy, with extensive resection of all involved bone and soft tissue. Preoperatively, proptosis was noted in 44 patients, 98% of whom improved. Twenty-eight patients (60%) had visual deficits before surgery, 21 (75%) of whom improved during follow-up. Visual field defect other than a central scotoma was the only prognostic factor for improvement in vision on multivariate analysis (p = 0.0062). Nine patients (19%) had recurrence or progression during follow-up. CONCLUSIONS: SOM is a unique skull base tumor that needs careful planning to optimize outcome. Aggressive removal of involved bone and periorbita is crucial, and proptosis and visual field defect other than a central scotoma can improve after surgery.

Gamma Knife radiosurgery for the treatment of Nelson's syndrome: a multicenter, international study.

OBJECTIVE: Nelson's syndrome is a rare and challenging neuroendocrine disorder, and it is associated with elevated adrenocorticotrophic hormone (ACTH) level, skin hyperpigmentation, and pituitary adenoma growth. Management options including resection and medical therapy are traditional approaches. Ionizing radiation in the form of Gamma Knife radiosurgery (GKRS) is also being utilized to treat Nelson's syndrome. In the current study the authors sought to better define the therapeutic role of stereotactic radiosurgery (SRS) in Nelson's syndrome. METHODS: Study patients with Nelson's syndrome were treated with single-fraction GKRS (median margin dose of 25 Gy) at 6 different centers as part of an International Radiosurgery Research Foundation (IRRF) investigation. Data including neurological function, endocrine response, and radiological tumor response were collected and sent to the study-coordinating center for review. Fifty-one patients with median endocrine and radiological follow-ups of 91 and 80.5 months from GKRS, respectively, were analyzed for endocrine remission, tumor control, and neurological outcome. Statistical methods were used to identify prognostic factors for these endpoints. RESULTS: At last follow-up, radiological tumor control was achieved in 92.15% of patients. Endocrine remission off medical management and reduction in pre-SRS ACTH level were achieved in 29.4% and 62.7% of patients, respectively. Improved remission rates were associated with a shorter time interval between resection and GKRS (p = 0.039). Hypopituitarism was seen in 21.6% and new visual deficits were demonstrated in 15.7% of patients. CONCLUSIONS: GKRS affords a high rate of pituitary adenoma control and improvement in ACTH level for the majority of Nelson's syndrome patients. Hypopituitarism is the most common adverse effect from GKRS in Nelson's syndrome patients and warrants longitudinal follow-up for detection and endocrine replacement.

Results of 1940 embolizations for dural arteriovenous fistulas: Japanese Registry of Neuroendovascular Therapy (JR-NET3).

OBJECTIVE: Embolization is the most common treatment for dural arteriovenous fistulas (dAVFs). A retrospective, multicenter observational study was conducted in Japan to clarify the nature, frequency, and risk factors for complications of dAVF embolization. METHODS: Patient data were derived from the Japanese Registry of Neuroendovascular Therapy 3 (JR-NET3). A total of 40,169 procedures were registered in JR-NET3, including 2121 procedures (5.28%) in which dAVFs were treated with embolization. After data extraction, the authors analyzed complication details and risk factors in 1940 procedures performed in 1458 patients with cranial dAVFs treated with successful or attempted embolization. RESULTS: Transarterial embolization (TAE) alone was performed in 858 cases (44%), and transvenous embolization (TVE) alone was performed in 910 cases (47%). Both TAE and TVE were performed in one session in 172 cases (9%). Complications occurred in 149 cases (7.7%). Thirty-day morbidity and mortality occurred in 55 cases (2.8%) and 16 cases (0.8%), respectively. Non-sinus-type locations, radical embolization as the strategy, procedure done at a hospital that performed dAVF embolization in fewer than 10 cases during the study period, and emergency procedures were independent risk factors for overall complications. CONCLUSIONS: Complication rates of dAVF embolization in Japan were acceptable. For better results, the risk factors identified in this study should be considered in treatment decisions.

Natural history of cavernous sinus meningiomas.

OBJECTIVEMeningiomas confined to the cavernous sinus (MCSs) are benign tumors. Due to the high risk of severe complications, the intracavernous surgical procedure was abandoned in favor of radiotherapy. However, the choice of treatment remains complicated due to the fact that the natural history of this lesion has not yet been described.METHODSThe authors studied the natural history of this lesion using a prospective series of 53 consecutive patients suffering from MCSs. The median follow-up duration was 10.2 years (range 2-25 years), from 1990 to 2016.RESULTSPatients ranged in age from 30 to 72 years (mean 53 years). The meningiomas were diagnosed by major symptoms (mainly oculomotor palsy and neuralgia experienced in 28 patients), minor symptoms (headache, intermittent diplopia in 15 patients), or incidental findings (10 patients). Simple symptomatic treatment (short courses of corticosteroids and carbamazepine) allowed patients to become asymptomatic in 19 (67.9%) of 28 cases experiencing major symptoms, and for 12 (80%) of 15 patients with initial minor symptoms (p < 0.0001). All patients with incidental findings remained asymptomatic. Forty four (83%) of 53 MCSs did not show any significant growth and 42 (80%) of 53 patients were not symptomatic at the end of follow-up (p < 0.001). The radiographic progression-free survival rates (± SD) at 5, 10, and 20 years were 90% ± 4.2%, 82% ± 5.7%, and 70% ± 10.2%, respectively. Five patients (9.4%) with no evidence of any effect of the initial medical treatment desired additional conventional radiation therapy.CONCLUSIONSBecause of the capricious, unpredictable, and slow growth of MCSs, together with high growth variability from one patient to the next, the symptomatic medical treatment of these tumors is a highly effective method. This series shows that these lesions are naturally, clinically, and radiologically indolent.

The medial wall of the cavernous sinus. Part 1: Surgical anatomy, ligaments, and surgical technique for its mobilization and/or resection.

OBJECTIVE: The medial wall of the cavernous sinus (CS) is often invaded by pituitary adenomas. Surgical mobilization and/or removal of the medial wall remains a challenge. METHODS: Endoscopic endonasal dissection was performed in 20 human cadaver heads. The configuration of the medial wall, its relationship to the internal carotid artery (ICA), and the ligamentous connections in between them were investigated in 40 CSs. RESULTS: The medial wall of the CS was confirmed to be an intact single layer of dura that is distinct from the capsule of the pituitary gland and the periosteal layer that forms the anterior wall of the CS. In 32.5% of hemispheres, the medial wall was indented by and/or well adhered to the cavernous ICA. The authors identified multiple ligamentous fibers that anchored the medial wall to other walls of the CS and/or to specific ICA segments. These parasellar ligaments were classified into 4 groups: 1) caroticoclinoid ligament, spanning from the medial wall and the middle clinoid toward the clinoid ICA segment and anterior clinoid process; 2) superior parasellar ligament, connecting the medial wall to the horizontal cavernous ICA and/or lateral wall of the CS; 3) inferior parasellar ligament, bridging the medial wall to the anterior wall of the CS or anterior surface of the short vertical segment of the cavernous ICA; and 4) posterior parasellar ligament, which anchors the medial wall to the short vertical segment of the cavernous ICA and/or the posterior carotid sulcus. The caroticoclinoid ligament and inferior parasellar ligament were present in most CSs (97.7% and 95%, respectively), while the superior and posterior parasellar ligaments were identified in approximately half of the CSs (57.5% and 45%, respectively). The caroticoclinoid ligament was the strongest and largest ligament, and it was typically assembled as a group of ligaments with a fan-like arrangement. The inferior parasellar ligament was the first to be encountered after opening the anterior wall of the CS during an interdural transcavernous approach. CONCLUSIONS: The authors introduce a classification of the parasellar ligaments and their role in anchoring the medial wall of the CS. These ligaments should be identified and transected to safely mobilize the medial wall away from the cavernous ICA during a transcavernous approach and for safe and complete resection of adenomas that selectively invade the medial wall.

Cavernous sinus compartments from the endoscopic endonasal approach: anatomical considerations and surgical relevance to adenoma surgery.

OBJECTIVE Tumors with cavernous sinus (CS) invasion represent a neurosurgical challenge. Increasing application of the endoscopic endonasal approach (EEA) requires a thorough understanding of the CS anatomy from an endonasal perspective. In this study, the authors aimed to develop a surgical anatomy-based classification of the CS and establish its utility for preoperative surgical planning and intraoperative guidance in adenoma surgery. METHODS Twenty-five colored silicon-injected human head specimens were used for endonasal and transcranial dissections of the CS. Pre- and postoperative MRI studies of 98 patients with pituitary adenoma with intraoperatively confirmed CS invasion were analyzed. RESULTS Four CS compartments are described based on their spatial relationship with the cavernous ICA: superior, posterior, inferior, and lateral. Each compartment has distinct boundaries and dural and neurovascular relationships: the superior compartment relates to the interclinoidal ligament and oculomotor nerve, the posterior compartment bears the gulfar segment of the abducens nerve and inferior hypophyseal artery, the inferior compartment contains the sympathetic nerve and distal cavernous abducens nerve, and the lateral compartment includes all cavernous cranial nerves and the inferolateral arterial trunk. Twenty-nine patients had a single compartment invaded, and 69 had multiple compartments involved. The most commonly invaded compartment was the superior (79 patients), followed by the posterior (n = 64), inferior (n = 45), and lateral (n = 23) compartments. Residual tumor rates by compartment were 79% in lateral, 17% in posterior, 14% in superior, and 11% in inferior. CONCLUSIONS The anatomy-based classification presented here complements current imaging-based classifications and may help to identify involved compartments both preoperatively and intraoperatively.

Hypofractionated stereotactic radiosurgery: a new treatment strategy for giant cavernous sinus hemangiomas.

OBJECTIVE Cavernous sinus hemangiomas (CSHs) are rare benign vascular tumors that arise from the dural venous sinuses lateral to the sella. Stereotactic radiosurgery (SRS) has emerged as a principal alternative to microresection for small- and medium-sized CSHs. Resection is a reasonable option for large (3-4 cm in diameter) and giant (> 4 cm in diameter) CSHs. However, management of giant CSHs remains a challenge for neurosurgeons because of the high rates of morbidity and even death that stem from uncontrollable and massive hemorrhage during surgery. The authors report here the results of their study on the use of hypofractionated SRS (H-SRS) to treat giant CSH. METHODS Between January 2008 and April 2014, 31 patients with a giant CSH (tumor volume > 40 cm3, > 4 cm in diameter) treated using CyberKnife radiosurgery were enrolled in a cohort study. Clinical status and targeted reduction of tumor volume were evaluated by means of serial MRI. The diagnosis for 27 patients was determined on the basis of typical imaging features. In 4 patients, the diagnosis of CSH was confirmed histopathologically. The median CSH volume was 64.4 cm3 (range 40.9-145.3 cm3). Three or 4 sessions of CyberKnife radiosurgery were used with a prescription dose based on the intent to cover the entire tumor with a higher dose while ensuring dose limitation to the visual pathways and brainstem. The median marginal dose to the tumor was 21 Gy (range 19.5-21 Gy) in 3 fractions for 11 patients and 22 Gy (range 18-22 Gy) in 4 fractions for 20 patients. RESULTS The median duration of follow-up was 30 months (range 6-78 months) for all patients. Follow-up MRI scans revealed a median tumor volume reduction of 88.1% (62.3%-99.4%) at last examination compared with the pretreatment volume. Ten patients developed new or aggravated temporary headache and 5 experienced vomiting during the treatment; these acute symptoms were relieved completely after steroid administration. Among the 30 patients with symptoms observed before treatment, 19 achieved complete symptomatic remission, and 11 had partial remission. One patient reported seizures, which were controlled after antiepileptic drug administration. No radiation-induced neurological deficits or delayed complications were reported during the follow-up period. CONCLUSIONS Hypofractionated SRS was an effective and safe modality for treating giant CSH. Considering the risks involved with microsurgery, it is possible that H-SRS might be able to serve as a definitive primary treatment option for giant CSH.

Prediction of cavernous sinus invasion in patients with Cushing's disease by magnetic resonance imaging.

OBJECTIVECavernous sinus invasion (CSI) in Cushing's disease (CD) negatively affects the probability of complete resection, biochemical cure, and need for adjuvant therapy. However, the prediction of CSI based on MRI findings has been inconsistent and variable. Among macroadenomas, the Knosp classification is the most widely utilized radiographic predictor of CSI, but its accuracy in predicting CSI and the probability of gross-total resection is limited in the setting of microadenomas or Knosp grade 0-2 macroadenomas. The authors noticed that the presence of a triangular shape of adenomas adjacent to the cavernous sinus on coronal MR images is frequently associated with CSI. The authors aimed to determine the correlation of this radiographic finding ("sail sign" [SS]) with CSI.METHODSThe authors performed a retrospective review of all patients with a pituitary lesion < 20 mm and a biochemical diagnosis of CD treated with endoscopic or microscopic transsphenoidal resection from November 2007 to May 2017. Overall 185 patients with CD were identified: 27 were excluded for negative preoperative imaging, 32 for lacking tumors adjacent to the sinus, 7 for Knosp grade 3 or higher, and 4 for inadequate intraoperative assessment of the CSI. Following application of inclusion and exclusion criteria, 115 cases were available for statistical analysis. Intraoperative CSI was prospectively evaluated at the time of surgery by one of two neurosurgical attending surgeons, and MRI data were evaluated retrospectively by a neurosurgical resident and attending neuroradiologist blinded to the intraoperative results.RESULTSA positive SS was identified in 23 patients (20%). Among patients with positive SS, 91% demonstrated CSI compared to 10% without an SS (p < 0.001). Using the SS as a predictor of CSI provided a sensitivity of 0.7 and a specificity of 0.98, with a positive predictive value (PPV) of 0.91 and a negative predictive value of 0.9. Among patients with positive SS, 30% did not achieve immediate postoperative remission, compared to 3.3% of patients without an SS (p < 0.001).CONCLUSIONSThe presence of a positive SS among Cushing's adenomas adjacent to the CS provides strong PPV, specificity, and positive likelihood ratio for the prediction of CSI. This can be a useful tool for preoperative planning and for predicting the likelihood of long-term biochemical remission and the need for adjuvant radiosurgery.

Upfront Gamma Knife radiosurgery for Cushing's disease and acromegaly: a multicenter, international study.

OBJECTIVE: Gamma Knife radiosurgery (GKS) is typically used after failed resection in patients with Cushing's disease (CD) and acromegaly. Little is known about the upfront role of GKS for patients with CD and acromegaly. In this study, the authors examine the outcome of upfront GKS for patients with these functioning adenomas. METHODS: An international group of 7 Gamma Knife centers sent pooled data from 46 patients (21 with CD and 25 with acromegaly) undergoing upfront GKS to the coordinating center of the study for analysis. Diagnosis was established on the basis of clinical, endocrine, and radiological studies. All patients were treated on a common radiosurgical platform and longitudinally followed for tumor control, endocrine remission, and hypopituitarism. Patients received a tumor median margin dose of 25 Gy (range 12-40.0 Gy) at a median isodose of 50%. RESULTS: The median endocrine follow-up was 69.5 months (range 9-246 months). Endocrine remission was achieved in 51% of the entire cohort, with 28% remission in acromegaly and 81% remission for those with CD at the 5-year interval. Patients with CD achieved remission earlier as compared to those with acromegaly (p = 0.0005). In patients post-GKS, the pituitary adenoma remained stable (39%) or reduced (61%) in size. Hypopituitarism occurred in 9 patients (19.6%), and 1 (2.2%) developed third cranial nerve (CN III) palsy. Eight patients needed further intervention, including repeat GKS in 6 and transsphenoidal surgery in 2. CONCLUSIONS: Upfront GKS resulted in good tumor control as well as a low rate of adverse radiation effects in the whole group. Patients with CD achieved a faster and far better remission rate after upfront GKS in comparison to patients with acromegaly. GKS can be considered as an upfront treatment in carefully selected patients with CD who are unwilling or unable to undergo resection, but it has a more limited role in acromegaly.

Clival chordomas: considerations after 16 years of endoscopic endonasal surgery.

OBJECTIVE In the past decade, the role of the endoscopic endonasal approach (EEA) has relevantly evolved for skull base tumors. In this study, the authors review their surgical experience with using an EEA in the treatment of clival chordomas, which are deep and infiltrative skull base lesions, and they highlight the advantages and limitations of this ventral approach. METHODS All consecutive cases of chordoma treated with an EEA between 1998 and 2015 at a single institution are included in this study. Preoperative assessment consisted of neuroimaging (MRI and CT with angiography sequences) and endocrinological, neurological, and ophthalmological evaluations, which were repeated 3 months after surgery and annually thereafter. Postoperative adjuvant therapies were considered. RESULTS Sixty-five patients (male/female ratio 1:0.9) were included in this study. The median age was 48 years (range 9-80 years). Gross-total resection (GTR) was achieved in 47 cases (58.7%). On univariate analysis, primary procedures (p = 0.001), location in the superior or middle third of the clivus (p = 0.043), extradural location (p = 0.035), and histology of conventional chordomas (p = 0.013) were associated with a higher rate of GTR. The complication rate was 15.1%, and there were no perioperative deaths. Most complications did not result in permanent sequelae and included 2 CSF leaks (2.5%), 5 transient cranial nerve VI palsies (6.2%), and 2 internal carotid artery injuries (2.5%), which were treated with coil occlusion of the internal carotid artery without neurological deficits. Three patients (3.8%) presented with complications resulting in permanent neurological deficits due to a postoperative hematoma (1.2%) causing a hemiparesis, and 2 permanent ophthalmoplegias (2.5%). Seventeen patients (26.2%) have died of tumor progression over the course of follow-up (median 52 months, range 7-159 months). Based on Kaplan-Meier analysis, the survival rate was 77% at 5 years and 57% at 10 years. On multivariate analysis, the extent of tumor removal (p = 0.001) and the absence of previous treatments (p = 0.001) proved to be correlated with a longer survival rate. CONCLUSIONS The EEA was associated with a high rate of tumor removal and symptom control, with low morbidity and preservation of a good quality of life. These results allow for a satisfactory overall survival rate, particularly after GTR and for primary surgery. Considering these results, the authors believe that an EEA can be a helpful tool in chordoma surgery, achieving a good balance between as much tumor removal as possible and the preservation of an acceptable patient quality of life.

Epidermoid cysts of the cavernous sinus: clinical features, surgical outcomes, and literature review.

OBJECTIVE: Epidermoid cysts of the cavernous sinus (CS) are rare, and no large case series of these lesions has been reported. In this study, the authors retrospectively reviewed the outcomes of the surgical management of CS epidermoid cysts undertaken at their center and performed a review of any such cysts reported in the literature over the past 40 years. METHODS: Clinical data were obtained on 31 patients with CS epidermoid cysts that had been surgically treated at the authors' hospital between 2001 and 2016. The patients' medical records, imaging data, and follow-up outcomes were retrospectively analyzed. The related literature from the past 40 years (18 articles, 20 patients) was also evaluated. RESULTS: The most common chief complaints were facial numbness or hypesthesia (64.5%), absent corneal reflex (45.2%), and abducens or oculomotor nerve deficit (35.5%). On MRI, 51.6% of the epidermoid cysts showed low T1 signals and equal or high T2 signals. In the other lesions, the radiological findings varied considerably given differences in the composition of the cysts. Surgery was performed via the extradural approach (58.1%), intradural approach (32.3%), or a combined approach (9.7%). After the operation, symptoms remained similar or improved in 90.3% of patients and new oculomotor paralysis developed after the operation in 9.7% of patients. Seven patients (22.6%) developed meningitis postoperatively (5 aseptic and 2 septic), and all of them recovered. All patients achieved good recovery before discharge (Karnofsky Performance Status score ≥ 70). Over an average follow-up of 4.6 ± 3.0 years in 25 patients (80.6%), no recurrence or reoperation occurred, regardless of whether total or subtotal resection of the capsule had been achieved. CONCLUSIONS: Both the extradural and intradural approaches can enable satisfactory lesion resection. A favorable prognosis and symptomatic improvement can be expected after both total and subtotal capsule resections. Total capsule resection is encouraged to minimize the possibility of recurrence provided that the resection can be safely performed.

The medial wall of the cavernous sinus. Part 2: Selective medial wall resection in 50 pituitary adenoma patients.

OBJECTIVE: Pituitary adenomas often invade the medial wall of the cavernous sinus (CS), but this structure is generally not surgically removed because of the risk of vascular and cranial nerve injury. The purpose of this study was to report the surgical outcomes in a large series of cases of invasive pituitary adenoma in which the medial wall of the CS was selectively removed following an anatomically based, stepwise surgical technique. METHODS: The authors' institutional database was reviewed to identify cases of pituitary adenoma with isolated invasion of the medial wall, based on an intraoperative evaluation, in which patients underwent an endoscopic endonasal approach with selective resection of the medial wall of the CS. Cases with CS invasion beyond the medial wall were excluded. Patient complications, resection, and remission rates were assessed. RESULTS: Fifty patients were eligible for this study, 15 (30%) with nonfunctional adenomas and 35 (70%) with functional adenomas, including 16 growth hormone-, 10 prolactin-, and 9 adrenocorticotropic hormone (ACTH)-secreting tumors. The average tumor size was 2.3 cm for nonfunctional and 1.3 cm for functional adenomas. Radiographically, 11 cases (22%) were Knosp grade 1, 23 (46%) Knosp grade 2, and 16 (32%) Knosp grade 3. Complete tumor resection, based on intraoperative impression and postoperative MRI, was achieved in all cases. The mean follow-up was 30 months (range 4-64 months) for patients with functional adenomas and 16 months (range 4-30 months) for those with nonfunctional adenomas. At last follow-up, complete biochemical remission (using current criteria) without adjuvant treatment was seen in 34 cases (97%) of functional adenoma. No imaging recurrences were seen in patients who had nonfunctional adenomas. A total of 57 medial walls were removed in 50 patients. Medial wall invasion was histologically confirmed in 93% of nonfunctional adenomas and 83% of functional adenomas. There were no deaths or internal carotid artery injuries, and the average blood loss was 378 ml. Four patients (8%) developed a new, transient cranial nerve palsy, and 2 of these patients required reoperation for blood clot evacuation and fat graft removal. There were no permanent cranial nerve palsies. CONCLUSIONS: The medial wall of the CS can be removed safely and effectively, with minimal morbidity and excellent resection and remission rates. Further follow-up is needed to determine the long-term results of this anatomically based technique, which should only be performed by very experienced endonasal skull base teams.

The oculomotor-tentorial triangle. Part 2: a microsurgical workspace for vascular lesions in the crural and ambient cisterns.

OBJECTIVEPathology in the region of the basilar quadrifurcation, anterolateral midbrain, medial tentorium, and interpeduncular and ambient cisterns may be accessed anteriorly via an orbitozygomatic (OZ) craniotomy. In Part 1 of this series, the authors explored the anatomy of the oculomotor-tentorial triangle (OTT). In Part 2, the versatility of the OTT as a surgical workspace for treating vascular pathology is demonstrated.METHODSSixty patients with 61 vascular pathologies treated within or via the OTT from 1998 to 2017 by the senior author were retrospectively reviewed. Patients were grouped together based on pathology/surgical procedure and included 1) aneurysms (n = 19); 2) posterior cerebral artery (PCA)/superior cerebellar artery (SCA) bypasses (n = 24); 3) brainstem cavernous malformations (CMs; n = 14); and 4) tentorial region dural arteriovenous fistulas (dAVFs; n = 4). The majority of patients were approached via an OZ craniotomy, wide sylvian fissure split, and temporal lobe mobilization to widen the OTT.RESULTSAneurysm locations included the P1-P2 junction (n = 7), P2A segment (n = 9), P2/3 (n = 2), and basilar quadrification (n = 1). Aneurysm treatments included clip reconstruction (n = 12), wrapping (n = 3), proximal occlusion (n = 2), and trapping with (n = 1) or without (n = 1) bypass. Pathologies in the bypass group included vertebrobasilar insufficiency (VBI; n = 3) and aneurysms of the basilar trunk (n = 13), basilar apex (n = 4), P1 PCA (n = 2), and s1 SCA (n = 2). Bypasses included M2 middle cerebral artery (MCA)-radial artery graft (RAG)-P2 PCA (n = 8), M2 MCA-saphenous vein graft (SVG)-P2 PCA (n = 3), superficial temporal artery (STA)-P2 PCA (n = 5) or STA-s1 SCA (n = 3), s1 SCA-P2 PCA (n = 1), V3 vertebral artery (VA)-RAG-s1 SCA (n = 1), V3 VA-SVG-P2 PCA (n = 1), anterior temporal artery-s1 SCA (n = 1), and external carotid artery (ECA)-SVG-s1 SCA (n = 1). CMs were located in the midbrain (n = 10) or pontomesencephalic junction (n = 4). dAVFs drained into the tentorial, superior petrosal, cavernous, and sphenobasal sinuses. High rates of aneurysm occlusion (79%), bypass patency (100%), complete CM resection (86%), and dAVF obliteration (100%) were obtained. The overall rate of permanent oculomotor nerve palsy was 8.3%. The majority of patients in the aneurysm (94%), CM (93%), and dAVF (100%) groups had stable or improved modified Rankin Scale scores.CONCLUSIONSThe OTT is an important anatomical triangle and surgical workspace for vascular lesions in and around the crural and ambient cisterns. The OTT can be used to approach a wide variety of vascular pathologies in the region of the basilar quadrifurcation and anterolateral midbrain.

Interrater and intrarater reliability of the Knosp scale for pituitary adenoma grading.

OBJECTIVE The goal of this study was to determine the interrater and intrarater reliability of the Knosp grading scale for predicting pituitary adenoma cavernous sinus (CS) involvement. METHODS Six independent raters (3 neurosurgery residents, 2 pituitary surgeons, and 1 neuroradiologist) participated in the study. Each rater scored 50 unique pituitary MRI scans (with contrast) of biopsy-proven pituitary adenoma. Reliabilities for the full scale were determined 3 ways: 1) using all 50 scans, 2) using scans with midrange scores versus end scores, and 3) using a dichotomized scale that reflects common clinical practice. The performance of resident raters was compared with that of faculty raters to assess the influence of training level on reliability. RESULTS Overall, the interrater reliability of the Knosp scale was "strong" (0.73, 95% CI 0.56-0.84). However, the percent agreement for all 6 reviewers was only 10% (26% for faculty members, 30% for residents). The reliability of the middle scores (i.e., average rated Knosp Grades 1 and 2) was "very weak" (0.18, 95% CI -0.27 to 0.56) and the percent agreement for all reviewers was only 5%. When the scale was dichotomized into tumors unlikely to have intraoperative CS involvement (Grades 0, 1, and 2) and those likely to have CS involvement (Grades 3 and 4), the reliability was "strong" (0.60, 95% CI 0.39-0.75) and the percent agreement for all raters improved to 60%. There was no significant difference in reliability between residents and faculty (residents 0.72, 95% CI 0.55-0.83 vs faculty 0.73, 95% CI 0.56-0.84). Intrarater reliability was moderate to strong and increased with the level of experience. CONCLUSIONS Although these findings suggest that the Knosp grading scale has acceptable interrater reliability overall, it raises important questions about the "very weak" reliability of the scale's middle grades. By dichotomizing the scale into clinically useful groups, the authors were able to address the poor reliability and percent agreement of the intermediate grades and to isolate the most important grades for use in surgical decision making (Grades 3 and 4). Authors of future pituitary surgery studies should consider reporting Knosp grades as dichotomized results rather than as the full scale to optimize the reliability of the scale.