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Background: While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown., Methods: Aptamer-based proteomics was performed on 147 CSF samples from 74 patients, 71 of whom had grade 2-4 astrocytomas or grade 2-3 oligodendrogliomas. This included pre- versus post-resection intracranial CSF samples obtained at early (1-16 days; n=20 patients) or delayed (86-153 days; n=11 patients) timepoints for patients with glioma. Paired lumbar-versus-intracranial glioma CSF samples were also obtained (n=14 patients)., Results: Significant differences were identified in the CSF proteome between lumbar, subarachnoid, and ventricular CSF from patients with gliomas. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome, with distinct sets of proteins present at different timepoints since resection. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, such as bevacizumab and immunotherapies., Conclusions: The intracranial glioma CSF proteome serves as a rich and dynamic reservoir of potential biomarkers that can be used to evaluate the effects of resection and other therapies over time. All data within this study, including detailed individual clinical annotations, are shared as a resource for the neuro-oncology community to collectively address these unanswered questions and further understand glioma biology through CSF proteomics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Purpose: Current methods for glioma response assessment are limited. This study aimed to assess the technical and clinical feasibility of molecular profiling using longitudinal intracranial CSF from patients with gliomas., Experimental Design: Adults with gliomas underwent longitudinal intracranial CSF collection via Ommaya reservoirs or ventriculoperitoneal shunts. cfDNA was extracted and analyzed using PredicineCARE for cancer variant profiling and/or PredicineSCORE for low-pass whole genome sequencing (LP-WGS)., Results: Five patients (2 females, 3 males; median age: 40 years, range 32-64 years) underwent longitudinal intracranial CSF collection via Ommaya reservoirs (n=4) or ventriculoperitoneal shunts (n=1). In total, forty-seven CSF samples were obtained (median volume: 4.00 mL; 0.5-5 mL). Forty-one samples (87.2%) yielded sufficient cfDNA for testing. Patient-specific tumor-associated variant allelic frequencies (VAFs), and thus tumor fraction, decreased in pre-versus-post chemoradiation samples, including through pseudoprogression. These also increased with radiographic progression in three patients, although identifying the time of definitive disease progression from MRIs was a significant limitation. In two patients with isocitrate dehydrogenase (IDH) mutant gliomas, decreasing IDH1 VAF after resection and chemoradiation correlated with decreased CSF D-2-hydroxyglutarate (D-2-HG) levels (0.64x and 0.62x, respectively, for the first patient, and 0.01x and 0.07x for the other patient), although D-2-HG and IDH1 VAF were not concordant in one patient thereafter. Moreover, CNB decreased below the limit of quantification during treatment and increased above the limit at progression., Conclusion: Longitudinal intracranial CSF cfDNA can feasibly be obtained in patients with gliomas during their disease course. Numerous questions and challenges should be answered before deploying this technique.

Stereotactic frameless needle brain biopsy is a common neurosurgical procedure performed via twist drill or open burr hole approaches. We aim to compare diagnostic yields and surgical outcomes to delineate the safety and efficacy of both approaches. A retrospective database of all stereotactic needle biopsy procedures performed at a single institution over 30 months was conglomerated. Demographics, medical comorbidities, operative details/complications, immediate post-operative imaging, and pathology were abstracted. Two hundred and twenty-five needle biopsies were identified, of which 165 (73.3%) were open, and 60 (26.7%) were twist drill. Diagnostic pathology yield rates between open (84.8%) and twist drill (93.3%) approaches were similar (p = 0.15), with a median of 4 cores taken in each (p = 0.30). Diagnostic tissue yields with an intra-operative pause for pathology confirmation was 90.4% compared to 79.1% without pause (p = 0.036, OR 2.49). Median operative times for open versus twist drill procedures were 68.0 min (IQR 49-83) versus 35.5 min (IQR 26-54), respectively (Wilcoxon p < 0.001), which remained significant after controlling for awaiting intraoperative pathology using bivariable linear modeling (p < 0.001). Intraoperative bleeding through the needle cannula was noted in 22 patients (9.8%), including eight twist drill (13.3%) and 14 open needles (8.5%). Of 197 cases (87.6%) with post-operative cranial imaging (CT/MRI), 90 (45.7%) demonstrated some degree of post-operative hemorrhage characterized as superficial (n = 10, 11.1%), deep/intralesional (n = 64, 71.1%) bleeding, or both (n = 16, 17.9%). Bleeding rates between open (46.7%) and twist drill (43.3%) approaches were similar (p = 0.78). Post-operative clinical decline or neurological change was noted in 9 patients (4.0%), including one twist drill (1.7%) and eight open needles (4.8%), among which 7 (78%) had deep blood products identified on post-operative imaging. Stereotactic needle biopsy via twist drill approach has similar diagnostic yield rates, asymptomatic bleeding rates, and post-operative complications with significantly shorter operative time and smaller incision size than conventional open burr hole needle biopsy. Using intra-operative frozen histopathology for presumed sufficient diagnostic tissue may improve final pathologic diagnostic rates regardless of approach technique., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Importance: Various invasive oculoplastic procedures are commonly utilized to control the rectus muscles and widen the surgical corridor through the endoscopic endonasal removal of large orbital apex cavernous hemangiomas (OACHs). They require additional transconjunctival incision, rectus muscle insertional retraction, or muscle deinsertion at the globe that might not be safe and lead to prolonged postoperative extraocular muscle dysfunction. In this article, the authors described a modified 3-handed extracapsular technique for the resection of a large OACH without an additional procedure for rectus muscle control. The aim is to achieve a safe gross total tumor removal while minimizing the procedure-related complications. An intraoperative video is included, along with a stepwise cadaveric dissection relevant to the approach., Clinical Presentation: A 71-year-old female presented with progressive left-sided blurred vision, binocular diplopia, and mild proptosis. Contrast-enhanced brain MRI revealed a large heterogeneous enhanced inferomedial intraconal mass in the left orbital apex, mostly consistent with cavernous hemangioma. Gross total tumor removal was achieved through a modified 3-handed endoscopic endonasal extracapsular approach. The diplopia was resolved, and significant visual improvement was achieved. Computed tomography scan demonstrated complete tumor removal, and histological examination confirmed the diagnosis., Conclusion: Endoscopic endonasal resection of large OACH can be feasibly performed by using a modified 3-handed extracapsular technique through the generous use of Q-tip swab applicators within the natural separation plane around the tumor capsule and a sequential traction-countertraction method. Subsequently, a gross total removal and optimal postoperative functional outcome are attainable through minimal rectus muscle fiber violation and intraconal fat manipulation., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Leiomyosarcoma (LMS) is a rare neoplasm that arises from tissues of embryonic mesodermal origin. Primary tissues of origin can include smooth muscle cells of the abdominopelvic viscera, blood vessels, or arrector pili muscles. LMS is known to metastasize to the lungs, with few reported cases of spread to the central nervous system., Observations: A 66-year-old male with cutaneous LMS of the left forearm with metastases to the lungs and kidney that had been treated with chemoradiation presented with worsening headaches. Magnetic resonance imaging revealed a sellar lesion. An endocrine workup was unremarkable. Imaging over 6 months revealed rapid interval growth. Positron emission tomography demonstrated moderate uptake. Given the rapid growth, the patient was offered an endoscopic endonasal approach for resection. Pathology confirmed LMS., Lessons: To the authors' knowledge, this is the first documented case of LMS metastasis to the sella. Pituitary carcinoma or metastases to the sellar region should be in the differential among patients with sellar region tumors with a rapid growth rate, bony erosion, or findings of lesions in the upper cervical lymph nodes or soft tissue. Tumors that show significant interval growth should raise suspicion for nonadenomatous lesions, and surgical intervention should be considered even in the absence of endocrinological dysfunction or cranial neuropathies. https://thejns.org/doi/10.3171/CASE2435.

Alpha-gal syndrome (AGS) is an immunoglobulin E-mediated hypersensitivity to galatcose-alpha-1,3-galactose (alpha-gal), a carbohydrate compound present in nonprimate mammalian products. Initial exposure to alpha-gal most often occurs through a tick bite, most commonly the lone star tick in the United States. Repeated exposure to alpha-gal may elicit severe allergic reactions, including anaphylaxis. The allergy restricts dietary intake and may significantly impact perioperative risk, as many medications, anesthetics, and intraoperative surgical products utilize bovine or porcine-derived agents, including those containing magnesium stearate, glycerol, and gelatin. Here, we review the perineurosurgical care of two individuals with AGS and highlight pertinent clinical practices and perioperative management of these patients., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples, including anatomical location and post-surgical changes, remains unknown. To that end, pre- versus post-resection intracranial CSF samples were obtained at early (1-16 days; n=20) or delayed (86-153 days; n=11) timepoints for patients with glioma. Paired lumbar-versus-intracranial glioma CSF samples were also obtained (n=14). Using aptamer-based proteomics, we identify significant differences in the CSF proteome between lumbar, subarachnoid, and ventricular CSF. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome. Proteomic data are provided with individual clinical annotations as a resource for the field., One Sentence Summary: Glioma cerebrospinal fluid (CSF) accessed intra-operatively and longitudinally via devices can reveal impacts of treatment and anatomical location.

Nervus intermedius (NI) arises from the superior salivary nucleus, solitary nucleus, and trigeminal tract. It leaves the pons as 1 to 5 roots and travels between the facial and vestibulocochlear nerves before merging with the facial nerve within the internal auditory canal. The mastoid segment of the facial nerve then gives rise to a sensory branch that supplies the posteroinferior wall of the external auditory meatus and inferior pina. This complex pathway renders the nerve susceptible to various pathologies, leading to NI neuralgia. Here, the authors present an unusual intraoperative finding of an atrophic NI in a patient with refractory NI neuralgia and a history of ipsilateral sudden-onset central facial palsy and microvascular decompression for trigeminal neuralgia. The patient underwent NI sectioning via the previous retrosigmoid window and achieved partial ear pain improvement. The gross size of the NI is compared with a cadaveric specimen through stepwise dissection. This case highlights the potential significance of subtle central ischemic events and subsequent atrophy of NI in the pathogenesis of NI neuralgia, as well as the ongoing need to investigate the therapeutic efficacy of nerve sectioning., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Schwannomas originating from the lower cranial nerves (LCNS) are rare and pose a significant surgical challenge. Resection is the mainstay treatment; however, risk of treatment morbidity is considerable, and the available literature regarding differential treatment outcomes in this vulnerable population is sparse., Methods: A single-institution cohort study and systematic literature review of LCNS were performed., Results: Fifty-eight patients were included: 34 underwent surgical resection and 24 underwent stereotactic radiosurgery (SRS). The median age at diagnosis was 48 years (range 17-74). Presenting symptoms were dysphagia (63%), dysarthria/hypophonia (47%), imbalance (33%), and hearing loss/tinnitus (30%). Tumor size was associated with surgical resection, as compared with initial SRS (4.1 cm vs 1.5 cm, P = .0001). Gross total resection was obtained in 52%, with tumor remnants predominantly localized to the jugular foramen (62%). Post-treatment worsening of symptoms occurred in 68% of surgical and 29% of SRS patients ( P = .003). Postoperative symptoms were mostly commonly hypophonia/hoarseness (63%) and dysphagia (59%). Seven patients (29%) had new neurological issues after SRS treatment, but symptoms were overall milder. The median follow-up was 60 months (range 12-252); 98% demonstrated meaningful clinical improvement. Eighteen surgical patients (53%) underwent adjuvant radiation at a median of 5 months after resection (range 2-32). At follow-up, tumor control was 97% in the surgical cohort and 96% among SRS patients., Conclusion: Although LCNS resection is potentially morbid, most postoperative deficits are transient, and patients achieve excellent tumor control-particularly when paired with adjuvant SRS. For minimally symptomatic patients undergoing surgical intervention, we advise maximally safe resection with intracapsular dissection to preserve nerve integrity where possible. For residual or as a primary treatment modality, SRS is associated with low morbidity and high rates of long-term tumor control., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Trigeminal neuralgia (TN) is characterized by paroxysmal episodes of severe shocklike orofacial pain typically resulting from arterial compression on the trigeminal root entry zone. However, neurovascular conflict in more proximal parts of the trigeminal pathway within the pons is extremely rare., Methods: The authors present a case of microvascular decompression for TN caused by dual arterial compression on the dorsolateral pons, along with a brief literature review., Results: Our patient was a 74-year-old man with episodic left-sided facial stabbing pain. Brain magnetic resonance imaging revealed a dual arterial compression on dorsolateral pons, the known site of the trigeminal sensory nucleus and descending trigeminal tract. Microvascular decompression was performed via a retrosigmoid approach. Complete pain relief and partial improvement of the facial hypesthesia were achieved immediately after surgery and the Barrow Neurological Institute (BNI) pain intensity score improved from V to I, and the BNI hypesthesia score decreased from III to II within a month following surgery. The literature review identified 1 case of TN secondary to an arteriovenous malformation in root entry zone with lateral pontine extension. One month following partial coagulation of the draining vein, the patient was reportedly able to reduce medication dosage by half to achieve an improvement of BNI pain intensity score from V to IIIa., Conclusions: Neurovascular compression in the trigeminal tract and nucleus is a rare but potential cause of TN. A thorough investigation of the trigeminal pathway should be considered during preoperative evaluation and intraoperative inspection, particularly if no clear offending vessel is identified., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hemifacial spasm is a neuromuscular disorder caused by compression of the facial nerve at the nerve root entry zone, often due to ectatic or aberrant vasculature. Pathologic compression of the nerve-brainstem interface results in involuntary, paroxysmal contractions of ipsilateral facial muscles that may cause considerable impairments in quality of life. For those with severe symptoms, have positive imaging demonstrating vascular compression, or who fail other management modalities, 1 2 3 4 microvascular decompression offers potential definitive treatment. 5 6 Traditionally, nonabsorbable packing agent is used to pack between the nerve and offending vascular structure. However, for large and more complex arterial structures, simple nonabsorbable padding is often not sufficient. In this operative video, we demonstrate microvascular decompression for intractable hemifacial spasm in a 52-year-old female using a specialized sling tacked to the petrous dura for management of a large, ectatic vertebral artery. Following a standard left retrosigmoid craniotomy, an atheromatous ectatic vertebral artery was identified. We fashioned a bovine pericardium sling around the vessel and used a permanent aneurysm clip to secure it to an incision portion of petrous dura. We subsequently identified potential additional facial nerve root compression by anterior inferior cerebellar artery (AICA) and posterior inferior cerebellar artery (PICA) branches, which were elevated and secured using Teflon felt packing. Following elevation of all three vessels, the lateral spread response resolved. At 2 weeks postoperatively, the patient reported substantial relief in her hemifacial spasms and endorsed highly improved quality of life., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Lesions located in the floor of the third ventricle are among the most difficult to access in neurosurgery. The neurovascular structures can limit transcranial exposure, whereas tumor extension into the third ventricle can limit visualization and access. The midline transsphenoidal route is an alternative approach to tumor invading the third ventricle if the tumor is localized at its anterior half and a working space between the optic apparatus and the pituitary infundibulum exists. The authors introduce the "infundibulochiasmatic angle," a valuable measurement supporting the feasibility of the translamina terminalis endoscopic endonasal approach (EEA) for resection of type IV craniopharyngiomas., Observations: Due to a favorable infundibulochiasmatic angle measurement on preoperative magnetic resonance imaging (MRI), an endoscopic endonasal transsellar transtubercular approach was performed to resect a type IV craniopharyngioma. At 2-month follow-up, the patient's neurological exam was unremarkable, with improvement in bitemporal hemianopsia. Postoperative MRI confirmed gross-total tumor resection., Lessons: The infundibulochiasmatic angle is a radiological tool for evaluating the feasibility of EEA when resecting tumors in the anterior half of the third ventricle. Advantages include reduced brain retraction and excellent rates of resection, with minimal postoperative risks of cerebrospinal fluid leakage and permanent pituitary dysfunction.

Background and Objectives: Vestibular schwannomas (VS) are often phenotypically benign lesions that may be technically challenging to resect because of involvement of neurovascular structures. The anterior inferior cerebellar artery (AICA) is commonly identified near VS, with variable position in relation to the tumor; however, little published literature describes anatomic and pathologic variants of AICA observed during VS resection., Methods: A prospectively maintained cohort of surgically managed VS with available operative reports and clinical/radiographic follow-up was queried and reviewed for noted aberrations., Results: We identified 66 cases with noted AICA abnormalities among 880 reviewer cases, including 20 loops extending into the internal auditory canal (2.3%), 18 arteries embedded in dura (2.0%), 15 AICA branches directly within VS (1.7%), 8 main trunk arteries coursing between cranial nerves 7 and 8 (0.9%), 3 arteries embedded in temporal bone (0.2%), 1 aneurysm (0.1%), and 1 artery bifurcating cranial nerve 6 (0.1%). The median age of AICA-variant patients was 55 years (range 19-74), and 29 were female (45%). Compared with the other AICA variants, tumors embedded with AICA tended to be larger lesions on maximal axial diameter (2.9 vs 1.6 cm; P = .006), they more commonly underwent less than total resection (73% vs 28%; P = .0001), and they had higher rates postoperative House-Brackmann scores >2 (47% vs 20%; P = .005). Two patients had radiographic and symptomatic postoperative cerebral ischemia or hemorrhage-1 from a bone-encased AICA and 1 from a dural embedded variant., Conclusion: Anatomic variants of AICA occur in approximately 7% of VS operations. Most aberrations do not affect surgical or clinical outcomes, and the rate of major vascular injury was low. However, certain types variably add operative time and in the case of AICA encasement in the tumor, likely indicate a more aggressive tumor phenotype with lower rates of gross total resection and high incidences of facial nerve weakness., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Calcified pseudoneoplasms of the neuraxis (CAPNONs) are rare, fibro-osseous lesions with an unknown cause that may present anywhere along the neuroaxis. Little is known about how intracranial CAPNONs present and about patients' long-term outcomes., Methods: A retrospective institutional review of intracranial pathology-confirmed CAPNONs was performed. Presenting clinical features, management, and clinical outcomes are highlighted. A literature review of intracranial CAPNON lesions was also performed to build on our series., Results: Ten patients were identified who met the inclusion criteria. Most patients presented with headaches (n = 6; 60%), seizures (n = 5; 50.0%), and neck and facial pain (n = 3; 30.0%). Most lesions were supratentorial (n = 7; 70.0%), with 3 infratentorial origins. Surgical resection was the most common initial management undertaken (n = 7; 70.0%). No new permanent postoperative neurologic deficits were identified. The median clinical and/or radiographic follow-up for all patients was 6.8 years (range, 0.7-23.3 years), with no recurrence of disease for 5 patients who underwent gross total resection. Four of 5 patients with residual or nonresectable lesions showed no interval growth on radiographic follow-up; 1 patient showed progression and worsening of presenting symptoms 2 months after resection. Resection substantially improved seizures and headaches in patients presenting with these symptoms (80% and 83.3%, respectively)., Conclusions: Intracranial CAPNONs may present with a wide variety of symptoms characteristic of the site of origin. The outcomes of these symptoms regarding survival and disease control are generally favorable, although resection does not always yield complete resolution of presenting deficits in certain patients, particularly those presenting with headaches or neck/facial pain., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction Every surgical trainee must acquire microsurgical skills within a limited timeframe. Therefore, identifying effective educational strategies to help learners attain these skills is crucial. Objective Establish the effectiveness of a low-fidelity microsurgery simulator to improve the execution and one's perception of the difficulty of basic surgical techniques. Methods From 2021 to 2022, 24 medical students were randomized to either (1) a treatment group (n=12) that engaged in longitudinal practice on a low-fidelity microsurgery simulator (the LazyBox) or (2) a control group (n=12) that did not practice. Students performed vessel loop ligation, catheter macroanastomosis, and synthetic vessel microanastomosis prior to and six weeks after intervention. Both objective metrics and subjective metrics (Swedish Occupational Fatigue Inventory (SOFI) and Surgery Task Load Index (SURG-TLX)) were obtained. Results The treatment and control arms had 1.2 (SD = 2.6) and 2.1 (SD = 2.4) points increase in the vessel loop ligation, respectively (p = 0.39). The treatment and control arms had a 3.4 (SD = 4.1) and 2.9 (SD = 3.6) points increase in the macroanastomosis task, respectively (p = 0.74). In the synthetic vessel microanastomosis task training, the experimental and control arms showed a 5.4 (SD = 8.3) and a 2.9 (SD = 5.6) points increase, respectively (p = 0.30). No differences were found between the groups regarding survey metrics of mental (p = 0.82), temporal (p = 0.23), and physical demands (p = 0.48). Conclusion In our randomized educational intervention, we found no significant difference in objective and subjective metrics of microsurgical task performance between learners who did and did not use the LazyBox simulator., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Jensen et al.)

High-grade gliomas are primary brain tumors that are incredibly refractory long-term to surgery and chemoradiation, with no proven durable salvage therapies for patients that have failed conventional treatments. Post-treatment, the latent glioma and its microenvironment are characterized by a senescent-like state of mitotic arrest and a senescence-associated secretory phenotype (SASP) induced by prior chemoradiation. Although senescence was once thought to be irreversible, recent evidence has demonstrated that cells may escape this state and re-enter the cell cycle, contributing to tumor recurrence. Moreover, senescent tumor cells could spur the growth of their non-senescent counterparts, thereby accelerating recurrence. In this review, we highlight emerging evidence supporting the use of senolytic agents to ablate latent, senescent-like cells that could contribute to tumor recurrence. We also discuss how senescent cell clearance can decrease the SASP within the tumor microenvironment thereby reducing tumor aggressiveness at recurrence. Finally, senolytics could improve the long-term sequelae of prior therapy on cognition and bone marrow function. We critically review the senolytic drugs currently under preclinical and clinical investigation and the potential challenges that may be associated with deploying senolytics against latent glioma. In conclusion, senescence in glioma and the microenvironment are critical and potential targets for delaying or preventing tumor recurrence and improving patient functional outcomes through senotherapeutics., (© 2023. The Author(s).)

Objective: The authors report a single-surgeon experience with anterior clinoid meningiomas (ACMs) and propose a novel scoring system to predict visual outcomes based on preoperative risk factors., Methods: A cohort study of all ACMs that were surgically treated by a single surgeon between 2003 and 2021 was performed. Visual function was assessed by an ophthalmologist pre- and postoperatively. Based on the combination of visual fields and visual acuity, 4 visual grades were described. Favorable visual outcomes were defined as mild visual deficit or intact vision postoperatively. Unfavorable visual outcomes were defined as a severe or moderate visual deficit. Predictors of unfavorable visual outcomes were identified using multivariable logistic regression analysis. A scoring system was then created using the resulting β coefficient. A receiver operating characteristic curve analysis was performed to identify a cutoff point on the grading score for stratifying patients at risk for unfavorable visual outcomes., Results: Fifty-two patients met all inclusion criteria. Twenty-five (48%) patients presented with intact vision, and 27 (51%) presented with some visual dysfunction. Postoperative favorable visual outcomes were achieved in 39 patients (75%). Among the 27 patients presenting with visual dysfunction, 14 (52%) experienced improvement after surgery. No new visual deficits were observed among the 25 patients with intact vision at baseline. Nine patients (17%) had a reversible complication. Multivariable analysis showed that severe preoperative visual deficit (OR 13.03, 95% CI 2.64-64.39; p = 0.002), radiographic evidence of optic nerve (ON) encasement (OR 4.20, 95% CI 1.06-16.61; p = 0.04), intraoperative evidence of ON invasion (OR 17.31, 95% CI 2.91-102.86; p = 0.002), an average ganglion cell layer thickness of ≤ 70 µm (OR 21.54, 95% CI 2.94-159.04; p = 0.003), and an average retinal nerve fiber layer thickness of ≤ 80 µm (OR 13.68, 95% CI 1.91-98.00; p = 0.009) were associated with unfavorable visual outcome. The predictive score included the following factors: abnormal optical coherence tomography (OCT) findings, radiographic evidence of ON encasement by the tumor, and severe preoperative visual deficit. A score ≥ 4 of 6 points was demonstrated to be the cutoff associated with unfavorable visual outcome, with a sensitivity of 80%, specificity of 88%, positive predictive value of 80%, negative predictive value of 88%, and area under the curve of 0.847 (95% CI 0.674-1.0; p = 0.003)., Conclusions: The authors have designed a practical and novel scoring system to predict visual outcomes in patients with ACMs. This scoring system may guide preoperative discussions with patients and timely surgical intervention to yield optimal visual function outcomes. Although most patients have excellent neurosurgical outcomes, severe baseline visual deficits, ON encasement, and characteristic OCT abnormalities are associated with unfavorable visual function after ACM resection.

Objective: The neurosurgery chief resident year is traditionally completed during the final residency year; however, a recent directive decried that enfolded fellowships should be undertaken following completion of the chief experience for most fellowships., Methods: A national survey was distributed to U.S.-based neurosurgery residency/fellowship directors regarding these changes., Results: We received 135 completed surveys (37% response rate). Respondents tended to feel the new post-chief enfolded fellowship mandate represented positive effects on residency training (58%) and chief experiences (54%)-overall, 47% agreed the changes are net positive, 17% neutral, and 36% negative. In addition, 66% respondents thought the enfolded fellowship was enhanced due to previous completion of the chief year. Most did not feel the directives had a negative impact on resident case minimums completion, total case volumes, or overall case mix during residency; but 64% felt it would reduce post-graduate training. Of those who said the mandate would reduce post-graduate training, 45% thought this would be positive. Throughout all questions, most respondents tended to feel strongly, although with little overall consensus across many of these questions. One area of relative agreement was a 60% preference to allow program discretion for chief/enfolded fellowship training timing-with 41% strongly supporting versus 15% strongly rejecting reversion to program-directed administration., Conclusions: Fervent bimodal opinions exist among residency program and fellowship directors regarding the directives for enfolded fellowships to follow successful completion of the chief resident experience. However, there was broad support for allowing greater program discretion for directing certain enfolded fellowship timing and structure., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Pediatric cerebrovascular lesions are very rare and include aneurysms, arteriovenous malformations (AVM), and vein of Galen malformations (VOGM)., Objective: To describe and disseminate a validated, reproducible set of 3D models for optimization of neurosurgical training with respect to pediatric cerebrovascular diseases METHODS: All pediatric cerebrovascular lesions treated at our institution with adequate imaging studies during the study period 2015-2020 were reviewed by the study team. Three major diagnostic groups were identified: aneurysm, AVM, and VOGM. For each group, a case deemed highly illustrative of the core diagnostic and therapeutic principles was selected by the lead and senior investigators for printing (CSG/JM). Files for model reproduction and free distribution were prepared for inclusion as Supplemental Materials., Results: Representative cases included a 7-month-old female with a giant left MCA aneurysm; a 3-day-old male with a large, complex, high-flow, choroidal-type VOGM, supplied from bilateral thalamic, choroidal, and pericallosal perforators, with drainage into a large prosencephalic vein; and a 7-year-old male with a left frontal AVM with one feeding arterial vessel from the anterior cerebral artery and one single draining vein into the superior sagittal sinus CONCLUSION: Pediatric cerebrovascular lesions are representative of rare but important neurosurgical diseases that require creative approaches for training optimization. As these lesions are quite rare, 3D-printed models and open source educational materials may provide a meaningful avenue for impactful clinical teaching with respect to a wide swath of uncommon or unusual neurosurgical diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Background: Surgical management of craniopharyngiomas is nuanced and has varied in terms of the selected approach and aggressiveness of resection over time. In the past several decades, the endoscopic transsphenoidal approach has become commonly used for craniopharyngioma resection. There is a well characterized institutional 'learning curve' regarding endoscopic transsphenoidal approaches for craniopharyngiomas at specialized centers; however, the broader global learning curve remains to be characterized., Methods: Clinical outcome data following endoscopic transsphenoidal craniopharyngioma resection were obtained from a previously published meta-analysis, including data published during or after the year 1990. Additionally, the year of publication, the country where procedures were performed, and the human development index of the country at time of publication were abstracted. Meta-regressional analyses were used to determine the significance of year and human development index as a covariate of the logit event rate of clinical outcomes. Statistical analyses were performed using the Comprehensive Meta-Analysis with a priori significance set as P < 0.05., Results: A total of 100 studies (8230 patients) were examined, representing data from 19 countries. There was a significant increase in the achieved gross total resection rate (P = 0.0002) and a decrease in the achieved partial resection rate (P < 0.0001) across the time studied. Additionally, the rate of visual worsening (P = 0.025), postoperative cerebrospinal fluid leaks (P = 0.007), and development of meningitis (P = 0.032) decreased across time., Conclusions: This work suggests the existence of a global learning curve when examining clinical outcomes following endoscopic transsphenoidal craniopharyngioma resection. Globally, these findings highlight a general improvement in clinical outcomes across time., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05-10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour., (© 2023. The Author(s).)

Competing Interests: None.

Introduction  Although many neuroanatomic atlases have been published, few have detailed complex cranial approaches and pertinent anatomic considerations in a stepwise fashion intended for rapid comprehension by neurosurgery students, residents, and fellows. Methods  Five sides of formalin-fixed latex-injected specimens were dissected under microscopic magnification. The frontotemporal and orbitozygomatic approaches were performed by neurosurgical residents and fellows at different training levels with limited previous experience in anatomical dissection mentored by the senior authors (M.P.C. and M.J.L.). Meticulous surgical anatomic dissections were performed until sufficient visual and technical completion was attained, with parameters of effectively demonstrating key surgical steps for educational training purposes. Following the completion of dissection and three-dimensional photography, illustrative case examples were reviewed to demonstrate the relative benefits and optimal applications of each approach. Results  The frontotemporal and orbitozygomatic approaches afford excellent access to anterior and middle skull base pathologies, as well as the exposure of the infratemporal fossa. Key considerations include head positioning, skin incision, scalp retraction, fat pad dissection and facial nerve protection, true or false MacCarty keyhole fashioning, sphenoid wing drilling and anterior clinoidectomy, completion of the craniotomy and accessory orbital osteotomy cuts, dural opening, and intradural neurovascular access. Conclusion  The frontotemporal and orbitozygomatic approaches are core craniotomies that offer distinct advantages for complex cranial operations. Learning and internalizing their key steps and nuanced applications in a clinical context is critical for trainees of many levels. The orbitozygomatic craniotomy in particular is a versatile but challenging approach; operative-style laboratory dissection is an essential component of its mastery and one that will be powerfully enhanced by the current work., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas 1,2 , no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples from consenting patients during their disease course via intra-operative collection and Ommaya reservoirs. D-2-HG and D/L-2-HG consistently decreased following tumor resection and throughout chemoradiation in patients monitored longitudinally. Our early experience with this strategy demonstrates the potential for intracranial CSF D-2-HG as a monitoring biomarker for IDH-mutant gliomas.

Nontraumatic perilesional aneurysms are thought to occur because of high-flow demands of feeding arteries and neoangiogenesis of hypervascular lesions, most commonly in vascular malformations, but they can rarely be associated with tumors as well. Most of these perilesional aneurysms are from intracranial vasculature associated with branches off the internal carotid artery. We report the unique case of a middle meningeal artery aneurysm associated with a giant convexity meningioma seen on a preoperative angiogram., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Mastery of microsurgical technique requires thousands of hours of deliberate practice, often with equipment that is not accessible to medical students. This study aimed to develop, test, and report a novel simulation system for providing medical students with early access to microsurgical technique., Methods: Low-cost, user-friendly, reusable microsurgery kits were iteratively developed using excess surgical supplies, such as catheter tubing and vessel loops. Students were tested on 2 separate tasks, with grading via a standardized performance scale incorporating aspects of alignment, leak, and anastomotic patency., Results: Twelve medical students were tested on standardized microsurgery kits at 2 different time points 6 weeks apart with no additional training received in between. Median change in total score on the vessel loop suturing task after 6 weeks was +2.6 points (range, -1.7 to +5 points); median change in completion time was -1.9 minutes (range, -3.5 to +2.7 minutes). Median change in total score on the red rubber anastomosis task was +5.8 points (range, -2.6 to +9.6 points) with a median improvement of -4.3 minutes (range, -9.6 to +2.6 minutes)., Conclusions: Reusable microsurgery kits designed with excess surgical supplies are educationally impactful tools that introduce medical students to microsurgical techniques early in their training, while also providing objective measures for skills acquisition over time., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pituitary abscess is a rare clinical entity, typically precipitated by Staphylococcus, Pseudomonas, or Aspergillus infection. Although Nocardia species-associated central nervous system abscesses have been documented in immunocompromised patients, no case of Nocardia pituitary abscesses has been previously reported., Observations: A 44-year-old man presented with hemoptysis and was found to have a cavitary right lung nodule, which was presumed histoplasmosis, prompting antifungal treatment. Several months later, he developed panhypopituitarism. Magnetic resonance imaging identified a pituitary mass, which subsequently underwent transsphenoidal endoscopic biopsy. Infectious workup was negative, and the patient was discharged on intravenous ertapenem therapy. Over several months, he developed progressive headaches, and updated imaging confirmed interval enlargement of the mass with new cavernous sinus invasion. He underwent repeat endoscopic biopsy, which yielded positive cultures for Nocardia farcinica and prompted successful treatment with trimethoprim-sulfamethoxazole and linezolid., Lessons: The current study highlights a previously unreported clinical entity, the first pituitary abscess attributable to Nocardia sp. or N. farcinica, which arose in a young, immunocompetent individual. Although rare, atypical infections represent an important component in the differential diagnosis for sellar mass lesions.

Objective: To perform a population-based study of pituitary adenoma epidemiology, including longitudinal trends in disease incidence, treatment patterns, and outcomes., Patients and Methods: In this study of incident pituitary adenomas in Olmsted County, Minnesota, from January 1, 1989, through December 31, 2019, we identified 785 patients who underwent primary screening, 435 of whom were confirmed as harboring incident pituitary adenomas and were included. Primary outcomes of interest included demographic characteristics, presenting features, and disease outcomes (tumor control, biochemical control, and complications)., Results: Among our 435 study patients, 438 unique pituitary adenomas were diagnosed at a median patient age of 39 years (interquartile range [IQR], 27 to 58 years). Adenomas were incidentally identified in 164 of the 438 tumors (37%). Common symptomatic presentations included hyperprolactinemia (188 of 438 [43%]) and visual field deficit (47 of 438 [11%]). Laboratory tests confirmed pituitary hormone hypersecretion in 238 of the 435 patients (55%), which was symptomatic in 222. The median tumor diameter was 8 mm (IQR, 5 to 17 mm). Primary management strategies were observation (156 of 438 tumors [36%]), medication (162 of 438 tumors [37%]), and transsphenoidal resection (120 of 438 tumors [27%]). Tumor and biochemical control were achieved in 398 (95%) and 216 (91%) secreting tumors, respectively. New posttreatment pituitary or visual deficits were noted in 43 (11%) and 8 (2%); apoplexy occurred in 28 (6%). Median clinical follow-up was 98 months (IQR, 47 to 189 months). Standardized incidence rates were 3.77 to 16.87 per 100,000 population, demonstrating linear expansion over time (R 2 =0.67). The mean overall standardized incidence rate was 10.1 per 100,000 population; final point prevalence was 175.1 per 100,000 population., Conclusion: Pituitary adenoma is a highly incident disease, with prolactin-secreting and incidental lesions representing the majority of tumors. Incidence rates and asymptomatic detection appear to be increasing over time. Presenting symptoms and treatment pathways are variable; however, most patients achieve favorable outcomes with observation or a single treatment modality., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: External ventricular drain (EVD) and intracranial pressure (ICP) monitor placements are among the most common critical care procedures for severe brain injury. Quality improvement initiatives have streamlined similar processes. The aim of the project was to decrease the time to collect supplies for EVD or ICP monitor placement by 25% by April 1, 2021., Methods: The project followed the define-measure-analyze-improve-control 6 sigma framework. Several quality gaps were identified: equipment stored separately, delays in replacing faulty items, and wasted resources. The team defined the process using the suppliers-inputs-processes-outputs-customers + requirements method, measured time to collect supplies, and analyzed data with an Ishikawa/fishbone diagram. The improve phase included a kaizen burst to generate solutions and an impact/effort grid to evaluate options. The team concluded that the optimal plan was to stock a mobile EVD cart and an ICP monitor pole with disposable go-bags., Results: The average time for nurses to collect EVD placement supplies decreased from 411 to 63 seconds (7-1 minute), and the average time for nurses to collect ICP monitor placement supplies decreased from 418 to 53 seconds (7-<1 minute). Residents decreased the time to obtain EVD placement supplies from 330 to 56 seconds (6-<1 minute) and ICP monitor supplies from 489 to 77 seconds (8-1 minute). Feedback was overwhelmingly positive and focused on improved process efficiency and reduced waste., Conclusions: The time reduction and enthusiasm are likely associated with the simplicity and comprehensiveness of the intervention design. Including key stakeholders in decision-making and succinct communications reduced resistance to change., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Glioblastoma (GBM) is a rapidly fatal malignancy typically treated with radiation and temozolomide (TMZ), an alkylating chemotherapeutic. These cytotoxic therapies cause oxidative stress and DNA damage, yielding a senescent-like state of replicative arrest in surviving tumor cells. Unfortunately, recurrence is inevitable and may be driven by surviving tumor cells eventually escaping senescence. A growing number of so-called "senolytic" drugs have been recently identified that are defined by their ability to selectively eliminate senescent cells. A growing inventory of senolytic drugs is under consideration for several diseases associated with aging, inflammation, DNA damage, as well as cancer. Ablation of senescent tumor cells after radiation and chemotherapy could help mitigate recurrence by decreasing the burden of residual tumor cells at risk of recurrence. This strategy has not been previously explored for GBM. We evaluated a panel of 10 previously described senolytic drugs to determine whether any could exhibit selective activity against human GBM persisting after exposure to radiation or TMZ. Three of the 10 drugs have known activity against BCL-XL and preferentially induced apoptosis in radiated or TMZ-treated glioma. This senolytic activity was observed in 12 of 12 human GBM cell lines. Efficacy could not be replicated with BCL-2 inhibition or senolytic agents acting against other putative senolytic targets. Knockdown of BCL-XL decreased survival of radiated GBM cells, whereas knockdown of BCL-2 or BCL-W yielded no senolytic effect., Implications: These findings imply that molecularly heterogeneous GBM lines share selective senescence-induced BCL-XL dependency increase the significance and translational relevance of the senolytic therapy for latent glioma., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background: Selection of skull base approaches is a critical skill for complex cranial surgery, which demands nuanced understanding of neuroanatomy and pathology., Objective: To develop novel pedagogical resources for approach selection education and assessment., Methods: A prospectively maintained skull base registry was screened for posterior fossa tumors amenable to 3-dimensional (3D) modeling of multiple operative approaches. Inclusion criteria were high-resolution preoperative and postoperative computed tomography and MRI studies (≤1 mm) and consensus that at least 3 posterior fossa craniotomies would provide feasible access. Cases were segmented using Mimics and modeled using 3-Matic. Clinical Vignettes, Approach Selection Questionnaire, and Clinical Application Questionnaire were compiled for implementation as a teaching/testing tool., Results: Seven cases were selected, each representing a major posterior fossa approach group. 3D models were rendered using clinical imaging for the primary operative approach, as well as a combination of laboratory neuroanatomic data and extrapolation from comparable craniotomies to generate 2 alternative approaches in each patient. Modeling data for 3D figures were uploaded to an open-sourced database in a platform-neutral fashion (.x3d) for virtual/augmented reality and 3D printing applications. A semitransparent model of each approach without pathology and with key deep structures visualized was also modeled and included for comprehensive understanding., Conclusion: We report a novel series of open-source 3D models for skull base approach selection training, with supplemental resources. To the best of our knowledge, this is the first such series designed for pedagogical purposes in skull base surgery or centered on open-source principles., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction  Skull base neuroanatomy is classically taught using surgical atlases. Although these texts are critical and rich resources for learning three-dimensional (3D) relationships between key structures, we believe they could be optimized and complemented with step-by-step anatomical dissections to fully meet the learning needs of trainees. Methods  Six sides of three formalin-fixed latex-injected specimens were dissected under microscopic magnification. A far lateral craniotomy was performed by each of three neurosurgery resident/fellow at varying stages of training. The study objective was the completion and photodocumentation of the craniotomy to accompany a stepwise description of the exposure to provide a comprehensive, intelligible, and anatomically oriented resource for trainees at any level. Illustrative case examples were prepared to supplement approach dissections. Results  The far lateral approach provides a wide and versatile corridor for posterior fossa operation, with access spanning the entire cerebellopontine angle (CPA), foramen magnum, and upper cervical region. Key Steps Include  The study includes the following steps: positioning and skin incision, myocutaneous flap, placement of burr holes and sigmoid trough, fashioning of the craniotomy bone flap, bilateral C1 laminectomy, occipital condyle/jugular tubercle drilling, and dural opening. Conclusion  Although more cumbersome than the retrosigmoid approach, a far lateral craniotomy offers unparalleled access to lesions centered lower or more medially in the CPA, as well as those with significant extension into the clival or foramen magnum regions. Dissection-based neuroanatomic guides to operative approaches provide a unique and rich resource for trainees to comprehend, prepare for, practice, and perform complex cranial operations, such as the far lateral craniotomy., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Introduction  Although endonasal endoscopic approaches (EEA) to the orbit have been previously reported, a didactic resource for educating neurosurgery and otolaryngology trainees regarding the pertinent anatomy, techniques, and decision-making pearls is lacking. Methods  Six sides of three formalin-fixed, color latex-injected cadaveric specimens were dissected using 4-mm 0- and 30-degree rigid endoscopes, as well as standard endoscopic equipment, and a high-speed surgical drill. The anatomical dissection was documented in stepwise three-dimensional (3D) endoscopic images. Following dissection, representative case applications were reviewed. Results  EEA to the orbit provides excellent access to the medial and inferior orbital regions. Key steps include positioning and preoperative considerations, middle turbinate medialization, uncinate process and ethmoid bulla removal, complete ethmoidectomy, sphenoidotomy, maxillary antrostomy, lamina papyracea resection, orbital apex and optic canal decompression, orbital floor resection, periorbita opening, dissection of the extraconal fat, and final exposure of the orbit contents via the medial-inferior recti corridor. Conclusion  EEA to the orbit is challenging, in particular for trainees unfamiliar with nasal and paranasal sinus anatomy. Operatively oriented neuroanatomy dissections are crucial didactic resources in preparation for practical endonasal applications in the operating room (OR). This approach provides optimal exposure to the inferior and medial orbit to treat a wide variety of pathologies. We describe a comprehensive step-by-step curriculum directed to any audience willing to master this endoscopic skull base approach., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: Vestibular schwannoma (VS) is a benign nerve-sheath tumor that sporadically displays aggressive behavior - often attributable to intrinsic tumor biology and an unfavorable immune microenvironment. However, the potential for idiosyncratic responses on VS growth to novel biologics is largely unknown., Methods: Case report., Results: A 57-year-old man underwent stereotactic radiosurgery (SRS) for a small intracanalicular presumed VS, which presented with left-sided hearing loss and episodic vertigo. Treatment response was excellent, with >50% reduction in tumor volume and confirmed stability at 14 years post-SRS radiographic follow-up. The patient subsequently developed an unrelated metastatic gastrointestinal tumor, and was started on tyrosine kinase inhibitors. Within 12-months of regorafenib treatment, and 16-years since SRS, the patient developed ipsilateral House-Brackmann Grade IV facial weakness. Dramatic VS expansion from 14 to 25 mm in maximum diameter, with new brain stem compression, was seen on MRI. Due to poor prognosis of his gastrointestinal malignancy, he declined surgical resection, and elected for palliative salvage SRS., Conclusion: We report the case of VS with radiographically proven stability for >14 years that underwent dramatic tumor progression after treatment with tyrosine kinase inhibitors. The dynamics between systemic immunomodulation and VS disease phenotype remain incompletely understood, and there may be potential for unintended iatrogenic VS progression., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Type-II odontoid fractures are common and highly morbid injuries, particularly among elderly patients. However, few risk stratification resources exist to predict outcomes and guide management decision making. Frailty indices have been increasingly utilized for these purposes in elective surgery, but have not been assessed for trauma. A single-center prospective trauma registry identified patients aged ≥ 80 years with type-II odontoid fractures. Frailty was the independent variable, using three independent indices: modified-5-item frailty (mFI-5), modified Charlson comorbidity (mCCI), and Davies. 97 patients had complete frailty data and sufficient follow up information, with median mIF-5 of 2 (range 0-4; 34 frail, mFI-5 > 2), median mCCI score of 6 (range 4-14), and median Davies score of 2 (range 0-7). For all indices, increasing score was associated with mortality, mIF-5 (HR = 1.76, 95%CI = 1.06-2.88), mCCI (HR = 1.10, 95%CI = 1.01-1.20), and Davies scores (HR = 1.21, 95%CI = 1.08-1.37). Median post-injury survival among patients with mIF-5 of ≤ 2 was 10-fold longer than patients with mIF-5 of > 2 (70 vs. 710 days, p = 0.0026). After adjusting for initial treatment strategy, frailty status remained an independent predictor of patient mortality; mIF-5 (HR = 1.72, 95%CI = 1.02-2.80), mCCI (HR = 1.10, 95%CI = 1.01-1.20), and Davies scores (HR = 1.21, 95%CI = 1.08-1.37). Among octogenarian patients with type-II odontoid fractures, frailty was associated with increased mortality, independent of treatment strategy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: The authors' objective was to reevaluate the role of microsurgery for epidermoid tumors by examining the associations between extent of resection (EOR), tumor control, and clinical outcomes., Methods: This was a retrospective study of patients with microsurgically treated intracranial epidermoid tumors. The recurrence-free and intervention-free rates were calculated using the Kaplan-Meier method. EOR was graded as gross-total resection (GTR) (total resection without residual on MRI), near-total resection (NTR) (a cyst lining was left in place), subtotal resection (STR) (> 90% resection), and partial resection (PR) (any other suboptimal resection) and used to stratify outcomes., Results: Sixty-three patients with mean clinical and radiological follow-up periods of 87.3 and 81.8 months, respectively, were included. Sixteen patients underwent second resections, and 5 underwent third resections. The rates of GTR/NTR, STR, and PR were 43%, 35%, and 22%, respectively, for the initial resections; 44%, 13%, and 44% for the second resections; and 40%, 0%, and 60% for the third resections (p < 0.001). The 5- and 10-year cumulative recurrence-free rates after initial resection were 64% and 32%, respectively. When stratified according to EOR, the 10-year recurrence-free rate after GTR/NTR was marginally better than that after STR (61% vs 35%, p = 0.130) and significantly better than that after PR (61% vs 0%, p < 0.001). The recurrence-free rates after initial microsurgery were marginally better than those after second surgery (p = 0.102) and third surgery (p = 0.065). The 5- and 10-year cumulative intervention-free rates after initial resection were 91% and 58%, respectively. When stratified according to EOR, the 10-year intervention-free rate after GTR/NTR was significantly better than that after STR (100% vs 51%, p = 0.022) and PR (100% vs 27%, p < 0.001). The 5-year intervention-free rate after initial surgery was marginally better than that after second surgery (52%, p = 0.088) and significantly better than that after third surgery (0%, p = 0.004). After initial, second, and third resections, permanent neurological complications were observed in 6 (10%), 1 (6%), and 1 (20%) patients, respectively. At the last follow-up visit, 82%, 23%, and 7% of patients were free from radiological recurrence after GTR/NTR, STR, and PR as the initial surgical procedure, respectively., Conclusions: GTR/NTR seems to contribute to better disease control without significantly impairing functional status. Initial resection offers the best chance to achieve better EOR, leading to better disease control.

Objective: Primary resection of adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma has become a front-line standard-of-care treatment for Cushing disease. However, surgical intervention can be challenging because of elevated blood pressure, as well as direct cortisol impacts on endothelial cells, vascular permeability, and tissue friability-potentially resulting in increased intraoperative bleeding. Tranexamic acid (TXA) is a well-studied, widely used intravenous hemostatic; however, the potential benefit during resection of ACTH-secreting pituitary adenoma is unstudied. The purpose of this study was to define an institutional protocol for perioperative administration of TXA in patients undergoing endoscopic endonasal approach for resection of ACTH-secreting pituitary adenoma, and to study the implementation of our novel protocol in a prospective fashion., Methods: Criteria for preoperative TXA were defined by age, medical history, and risk factors. Descriptive statistics were reported for all patients receiving perioperative TXA., Results: Thirty patients met inclusion criteria and underwent perioperative administration of TXA, using a standardized dosing protocol of a 10 mg/kg bolus in 30 minutes prior to incision, followed by maintenance infusion of 2 mg/kg/hour for the duration of the procedure. No incidence of myocardial infarction or postoperative thromboembolic events were noted. Subjective assessments indicated satisfaction with the patient selection protocol, and meaningful reduction in the extent of intraoperative bleeding., Conclusions: Perioperative TXA represents a potentially efficacious approach for control of intraoperative bleeding during endonasal resection of ACTH-secreting tumors. Careful preoperative patient selection is emphasized, given the potential for thromboembolic complications; however, initial experience with our institutional protocol suggests a favorable risk/benefit profile when this treatment is applied judiciously., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Importance: Progressive episodic spells of altered levels of consciousness, often advancing to include paroxysmal autonomic instability, may be indicative of a diencephalic dysfunction underlying spontaneous intracranial hypotension (SIH). A rare, and often indolent, etiology may be spinal cerebrospinal fluid (CSF) leak-an elusive diagnosis, especially in cases of CSF-venous fistula (CVF) that are often missed on routine computed tomography (CT) myelography and magnetic resonance imaging (MRI)., Clinical Presentation: We report an unusual case of a 50-yr-old woman who presented with rapidly progressive cyclical, self-resolving episodes of altered mentation and decreased arousal later in the day. Scrutiny of serial brain MRIs led to a diagnosis of SIH, with severe downward diencephalic and brain stem displacement-resulting in cerebral aqueduct occlusion with obstructive hydrocephalus. Initial clinical improvement occurred with CSF diversion, but the patient quickly deteriorated-developing diencephalic spells, including extensor posturing and severely depressed levels of consciousness. Clinical improvement was seen with stopping CSF diversion and Trendelenburg-positioning. After intensive spinal imaging, dynamic CT myelography identified a left T10 nerve root diverticula and CSF-venous fistula. Surgical obliteration resulted in rapid, profound neurological improvement, and ultimately full neurological recovery by 1 yr., Conclusion: In our patient, worsening episodes of confusion, postural headaches, and autonomic instability developed due to SIH, which induced profound downward displacement and compression of the diencephalon and brain stem, and accompanied by subsequent obstructive hydrocephalus. Diagnostic persistence identified the CVF, which had caused the complex multifold pathophysiology and clinical presentation. If suspicion remains high for CVF, persistent spinal imaging, particularly with dynamic myelography, may be crucial., (© Congress of Neurological Surgeons 2021.)

Objective  This study was aimed to provide a key update to the seminal works of Prof. Albert L. Rhoton Jr., MD, with particular attention to previously unpublished insights from the oral tradition of his fellows, recent technological advances including endoscopy, and high-dynamic range (HDR) photodocumentation, and, local improvements in technique, we have developed to optimize efficient neuroanatomic study. Methods  Two formaldehyde-fixed cadaveric heads were injected with colored latex to demonstrate step-by-step specimen preparation for microscopic or endoscopic dissection. One formaldehyde-fixed brain was utilized to demonstrate optimal three-dimensional (3D) photodocumentation techniques. Results  Key steps of specimen preparation include vessel cannulation and securing, serial tap water flushing, specimen drainage, vessel injection with optimized and color-augmented latex material, and storage in 70% ethanol. Optimizations for photodocumentation included the incorporation of dry black drop cloth and covering materials, an imaging-oriented approach to specimen positioning and illumination, and single-camera stereoscopic capture techniques, emphasizing the three-exposure-times-per-eye approach to generating images for HDR postprocessing. Recommended tools, materials, and technical nuances were emphasized throughout. Relative advantages and limitations of major 3D projection systems were comparatively assessed, with sensitivity to audience size and purpose specific recommendations. Conclusion  We describe the first consolidated step-by-step approach to advanced neuroanatomy, including specimen preparation, dissection, and 3D photodocumentation, supplemented by previously unpublished insights from the Rhoton fellowship experience and lessons learned in our laboratories in the past years such that Prof. Rhoton's model can be realized, reproduced, and expanded upon in surgical neuroanatomy laboratories worldwide., Competing Interests: Conflict of Interest L.P.C. reports grants from Mayo Foundation, during the conduct of the study. M.P.C. reports grants from NREF, grants from Medtronic, grants from Storz, grants from CAPES, grants from Mayo Foundation, during the conduct of the study. L.C.P.C.L. reports grants from CAPES, during the conduct of the study.A.P. reports grants from Mayo Clinic, during the conduct of the study. M.J.L. reports grants from Mayo Foundation, during the conduct of the study., (Thieme. All rights reserved.)

Introduction  Neurosurgical anatomy is traditionally taught via anatomic and operative atlases; however, these resources present the skull base using views that emphasize three-dimensional (3D) relationships rather than operative perspectives, and are frequently written above a typical resident's understanding. Our objective is to describe, step-by-step, a retrosigmoid approach dissection, in a way that is educationally valuable for trainees at numerous levels. Methods  Six sides of three formalin-fixed latex-injected specimens were dissected under microscopic magnification. A retrosigmoid was performed by each of three neurosurgery residents, under supervision by the senior authors (C.L.W.D. and M.J.L.) and a graduated skull base fellow, neurosurgeon, and neuroanatomist (M.P.C.). Dissections were supplemented with representative case applications. Results  The retrosigmoid craniotomy (aka lateral suboccipital approach) affords excellent access to cranial nerve (CN) IV to XII, with corresponding applicability to numerous posterior fossa operations. Key steps include positioning and skin incision, scalp and muscle flaps, burr hole and parasigmoid trough, craniotomy flap elevation, initial durotomy and deep cistern access, completion durotomy, and final exposure. Conclusion  The retrosigmoid craniotomy is a workhorse skull base exposure, particularly for lesions located predominantly in the cerebellopontine angle. Operatively oriented neuroanatomy dissections provide trainees with a critical foundation for learning this fundamental skull base technique. We outline a comprehensive approach for neurosurgery residents to develop their familiarity with the retrosigmoid craniotomy in the cadaver laboratory in a way that simultaneously informs rapid learning in the operating room, and an understanding of its potential for wide clinical application to skull base diseases., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: Sialadenitis is a rare complication of skull base neurosurgery, in which the submandibular gland undergoes acute inflammation with edema after surgery. Although attributable to transient obstruction or manual compression, presentation may be rapidly life-threatening as a result of airway obstruction. Understanding risk factors is limited at present, and no practical management guidelines have been reported. Our objective was to survey the literature and to characterize the associated risk factors, treatment considerations, and overall trends in outcomes for patients experiencing post skull base neurosurgery sialadenitis., Methods: A search of the Ovid EMBASE, SCOPUS, and PubMed databases from inception through August 2020 was performed via Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Systematic review identified 13 publications describing 18 cases of acute sialadenitis after skull base surgery. We describe the 19th reported case. Commonalities include the need for aggressive respiratory support as intubation or emergent tracheostomy is almost universally required. Risk factors are poorly understood but may include extreme flexion and/or rotation of the head and neck. Outcomes are favorable overall, although secondary complications have been described., Conclusions: Sialadenitis is a rare but potentially life-threatening complication of skull base neurosurgery, owing to acute loss of airway and the potential for a diverse array of secondary complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective  Cerebrovascular complications (CVC) are rare consequences of vestibular schwannoma (VS) surgery. Our objective was to assess incidences of findings suggestive of postoperative CVC in a large single surgeon cohort, as well as potential risk factors, and implications. Study Design  A cohort of 591 patients was retrospectively reviewed. Postoperative magnetic resonance images were screened for findings suggestive of stroke, T2 hyperintensity in the cerebellopontine angle structures or new encephalomalacia. Clinical records were queried for findings consistent with postoperative CVC. Results  In total, 61 patients had radiographic findings consistent with possible postoperative CVC (10%); of them, eight had documented intraoperative vascular injury (1.4%), and four had postoperative clinical exam changes indicative of CVC (0.7%). Clinically manifest intraoperative vascular injuries occurred in four patients and involved the petrosal venous complex ( n  = 3, 5%) or anterior inferior cerebellar artery ( n  = 1, 2%); clinical deficits included hemiparesis ( n  = 1, 2%), facial anesthesia ( n  = 2, 4%), dysphagia ( n  = 2, 2%), and unfavorable facial nerve function in two (50%). Three out of four patients in this group required out-of-home placement (75%). Clinical CVCs ( n  = 4) were not significantly associated with tumor size, tumor cyst, gross total resection, or length of stay. Patients with clinical CVC were significantly more likely to require posthospitalization rehabilitation (19 vs. 75%, p  = 0.02; 14 vs. 100%, p  = 0.0002). Conclusion  Although radiographic findings suggestive of CVC were unexpectedly common in this cohort, intraoperative vascular injury and postoperative clinical CVC were exceedingly rare. The association between unfavorable facial nerve outcome and clinical CVC is likely a marker for more difficult operations, predisposing to higher risk of complications., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

A 25-year-old man presented with left-sided hearing loss, blurred vision and papilloedema. Imaging revealed a large, left-sided, contrast-enhancing cerebellopontine mass causing obstructive hydrocephalus, consistent with vestibular schwannoma (VS). Following an incomplete resection via retrosigmoid craniotomy at an outside facility, he was referred to our department, and cerebrospinal fluid diversion followed by repeat resection was recommended. A subtotal resection was achieved, and the patient was subsequently treated with adjuvant stereotactic radiosurgery (SRS). Progressive interval growth was observed on serial post-SRS MRI studies; correspondingly, at 31 months after treatment, the patient was initiated on antiprogrammed-death receptor 1 (PD-1) antibody treatment with pembrolizumab. Growth arrest was noted on subsequent serial imaging studies, which have been maintained for a total of 30 months since initiation of a 18-month anti-PD-1 course of therapy. Additional case accumulation and translational study is required to better characterise this therapeutic strategy; however, PD-1/programmed death-ligand 1 inhibition may offer a promising salvage therapy for refractory VS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Penetrating spinal cord injuries are rare in children but result in devastating impacts on long-term morbidity and mortality-with little known about the recovery capacity in this age group. We present the case of an eight-year-old child who sustained a penetrating injury through the right anterior thorax. Thoracic CT showed the arrow tip extending through the spinal canal at T6. Neurologic examination revealed no motor or sensory function below T6. The arrow was surgically removed without complications through an anterior-only approach. MRI on post-operative day (POD) 4 showed focal T2 hyperintensity at the T6 spinal cord. Patient was discharged on POD33 with an American Spinal Injury Association (ASIA)-D score and trace voluntary control over bowel and bladder function. Remarkably, four months later, he had near normal bowel and bladder function, with near-intact lower extremity strength and self-sustained ambulation. Follow-up imaging revealed hemicord formation at the level of injury. We review our case of penetrating spinal cord injury in a child and similar reports in the literature. Penetrating thoracic spinal cord trauma portends poor clinical outcomes, particularly when employing available adult prognostic spinal cord injury scoring metrics. Incomplete spinal cord injury, and often-associated spinal shock, can mimic a complete injury-as in our patient, which improved to near-complete motor and sensory restoration of function and resulted in the formation of a split hemicord. This case represents a unique penetrating spinal cord injury with remarkable neurologic recovery, which would advocate against definitive early prognostication in the pediatric population.

Background: The lateral craniopharyngeal or Sternberg's canal (SC) originates from superior orbital fissure (SOF) and traverses the sphenoid body into the nasopharynx. A remnant of the canal, Sternberg's defect (SD), has been debated as a source of cerebrospinal fluid (CSF) leak. The canal was described in 1888, and there is limited accurate visual illustration in the literature., Objective: To provide a detailed anatomic and radiological illustration of the canal in pediatric and adult population including the mechanism undermining the incidence of the canal, and the possibility of the canal as a source of CSF leak., Methods: A total of 195 high-resolution computed tomographies (CT) of patients (50 3-yr-old, 20 5-yr-old, and 125 adults) and 43 dry adult skulls (86 sides) were analyzed for a canal matching the description of the SC., Results: A SC was identified in 86% of the 3-yr-old and 40% of 5-yr-old patients. The diameter and length were 2.12 mm and 12 mm, respectively. The incidence of the canal decreased with age as sinus pneumatization extended into the sphenoid sinus. Only 0.8% of the adult skull on CT had the canal. The canal was not present on the dry adult skulls examination, but SD was found in 4.65%., Conclusion: SC exists with high incidence in the pediatric group. Sinus pneumatization obliterates the canal in the adult population, leaving a defect in 4.65% of cases, which given the location and related anatomic structures, is unlikely to be a source of CSF leak., (© Congress of Neurological Surgeons 2021.)

Introduction  The middle fossa (MF) approaches encompass a group of versatile surgical accesses to pathologies in the MF, internal auditory canal (IAC), and superomedial aspect of the posterior fossa. Although many descriptions of the MF approaches have been published, a practical surgical guide that allows an easy understanding for Skull Base trainees is needed. Methods  Three formalin-fixed, colored-injected specimens were dissected under microscopic magnification (six sides). A MF craniotomy followed by IAC drilling was performed on three sides, and anterior petrosectomy (AP) was performed in the remaining three sides. The anatomical dissection was documented in stepwise three-dimensional photographic images. Following dissection, representative case applications were reviewed. Results  The MF approach provides direct access to the MF structures and IAC. The AP provides excellent access to the superomedial aspect of the posterior fossa. Key common steps include: positioning and skin incision; scalp and muscle flaps; burr holes; craniotomy flap elevation; dural dissection along the petrous ridge; division of the middle meningeal artery; and exposure of the greater superficial petrosal nerve, tegmen tympani, and V3. Then, to approach the IAC: superior IAC drilling, and longitudinal dura opening. The area drilled in the AP approach forms a pentagon limited by the petrous internal carotid artery, cochlea, IAC, petrous ridge, and lateral border of V3. Conclusion  The MF approaches are challenging. Operatively oriented skull base dissections provide a crucial foundation for learning these techniques. We describe comprehensive step-by-step approaches intended to develop familiarity in the cadaver laboratory and facilitate understanding of their potential for skull base disorders. Basic surgical principles are described to help in the operating room as well as illustrative cases., Competing Interests: Conflict of Interest Educational grants from NREF, Zeiss, Medtronic, and Storz. Dr. Peris-Celda, Dr. Salgado-Lopez, and Dr. Pereira Campos Leonel report grants from NREF, Medtronic, and Storz during the conduct of the study., (Thieme. All rights reserved.)