Neurosurgical Management of Patients with Alpha-Gal Syndrome.

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.

Anatomical Step-by-Step Dissection of Complex Skull Base Approaches for Trainees: Surgical Anatomy of the Frontotemporal and Orbitozygomatic Craniotomies.

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.

Radiation-Associated Vestibular Schwannomas: Case Series and Literature Review.

OBJECTIVES: Radiation treatment, particularly at a young age, creates theoretical risk for long-term adverse radiation effects, including the development of malignancy. The literature is sparse on radiation-induced vestibular schwannomas (VSs). METHODS: A retrospective review was performed for cases of suspected radiation-induced VS at 2 high-volume centers. Only cases where radiation included coverage of the posterior fossa were included with those diagnosed within 3 years of radiation treatment being excluded. Patient and tumor characteristics were collected. A systematic literature review was also performed for any previously published series on radiation-induced VS. RESULTS: Eight cases of radiation-induced VS were identified with a median follow-up 125 months (range 7-131). The median age at incident radiation was 15 years (range 2-46). The median age at VS diagnosis was 57 years (range 26-83) with median interval from radiation to diagnosis of 51-years (range 15-66). The median tumor size was 6 mm (range 3-21). Two patients underwent surgical resection. Lesions were described as soft and highly vascular, with medium to high adherence to the facial nerve. Five articles with a total of 52 patients were identified, median age at VS diagnosis was 42-years (range 23-73) with a median interval from radiation to diagnosis of 19 years (range 15-23). CONCLUSIONS: The development of VS following radiation exposure appears rare and our understanding of the condition remains incomplete. Further studies are required to determine the best management of these patients and determine whether there is a causative relationship between radiation exposure and the development of VS.

The dynamic impact of location and resection on the glioma CSF proteome.

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.

Modified Function-Preserving Endoscopic Endonasal Extracapsular Resection of a Large Orbital Apex Cavernous Hemangioma.

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.

Unusual Atrophic Nervus Intermedius in a Patient with Refractory Nervus Intermedius Neuralgia and History of Ipsilateral Sudden-Onset Central Facial Palsy and Sensorineural Hearing Loss: Cadaveric-Clinical Images with Surgical Video.

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.

Surgical Treatment of Hemifacial Spasm via Microvascular Decompression of a Large, Ectatic Vertebral Artery.

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.

The infundibulochiasmatic angle and the favorability of an endoscopic endonasal approach in type IV craniopharyngioma: illustrative case.

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.

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

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

Lower Cranial Nerve Schwannomas: Cohort Study and Systematic Review.

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.

Angiographic cross-filling between inferior petrosal sinuses and alteration of adrenocorticotropic hormone sampling results for tumor localization in Cushing disease.

OBJECTIVE: Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to guide diagnostic localization of imaging-negative adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas. However, the efficacy of IPSS has been suboptimal at accurately lateralizing the adenoma, reducing surgical cure rates and leading to unintended pituitary dysfunction due to the added exploration. One rationale for the occasional imprecision is the existence of additional petrosal sinus collateral channels that connect the IPS bilaterally, which may lead to false localization results during sampling. The aim of this study was to explore a potential connection between normal anatomical variation in the angioarchitecture of the IPSs and the ACTH results obtained in subsequent IPSS tests. METHODS: A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPSS for radiographically equivocal pituitary microadenomas. Cases were reviewed for tumor laterality noted on either operative or pathology reports, as well as the presence of angiographic evidence of cross-filling between the sinuses. In addition, ACTH levels from the right and left IPSs were documented at baseline and at 2, 5, and 10 minutes after corticotropin-releasing hormone (CRH) administration. A ratio of the change in ACTH levels measured at the time of maximal response (10 minutes) versus the levels measured at the initial response (2 minutes) was computed for each patient and compared between patients by their angiographic cross-filling status. RESULTS: There were 41 patients with a histopathologically confirmed right- or left-sided ACTH-secreting pituitary microadenoma who underwent preoperative IPSS. Among these patients, 28 (68%) showed angiographic evidence of cross-filling between the IPSs, and 13 showed no cross-filling. On average, ACTH levels increased by a factor of 3.91 ± 0.77 in the contralateral IPS in patients with angiographic cross-filling, compared with a factor increase of only 1.80 ± 0.27 in patients without cross-filling (p = 0.014). In comparison, ACTH levels increased by a factor of 2.01 ± 0.57 in the ipsilateral IPS in patients with cross-filling, and by 8.78 ± 7.30 in those without cross-filling (p = 0.373). CONCLUSIONS: The presence of angiographic cross-filling, suggestive of a greater degree of vascular channel networking between the right and left IPS, is a significant factor influencing the measured rates of change of ACTH in IPSS and may impact the specificity of this test to accurately determine microadenoma laterality in the preoperative setting.

Microvascular Decompression for Trigeminal Neuralgia Caused by Vascular Compression on the Trigeminal Sensory Nucleus and Descending Trigeminal Tract.

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.

Anterior clinoid meningiomas: surgical results and proposed scoring system to predict visual outcomes.

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 ß 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.

An untapped window of opportunity for glioma: targeting therapy-induced senescence prior to recurrence.

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.

Calcifying Pseudoneoplasm of the Neuraxis: An Institutional Series of Ten Cases and Review of the Literature to Date.

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.

Anatomic Variants in the Anterior Inferior Cerebellar Artery Encountered During Resection of Vestibular Schwannomas.

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.

Improvements in the Endoscopic Transsphenoidal Resection of Craniopharyngiomas: A Global Learning Curve.

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.

Assessing the Impact of Shifting Enfolded Neurosurgery Fellowships to Follow the Chief Resident Experience: National Survey of Program and Fellowship Directors.

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.

Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas.

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.

That which is unseen: 3D printing for pediatric cerebrovascular education.

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.