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.

Prediction of Surgical Outcomes in Normal Pressure Hydrocephalus by MR Elastography.

BACKGROUND AND PURPOSE: Normal pressure hydrocephalus is a treatable cause of dementia associated with distinct mechanical property signatures in the brain as measured by MR elastography. In this study, we tested the hypothesis that specific anatomic features of normal pressure hydrocephalus are associated with unique mechanical property alterations. Then, we tested the hypothesis that summary measures of these mechanical signatures can be used to predict clinical outcomes. MATERIALS AND METHODS: MR elastography and structural imaging were performed in 128 patients with suspected normal pressure hydrocephalus and 44 control participants. Patients were categorized into 4 subgroups based on their anatomic features. Surgery outcome was acquired for 68 patients. Voxelwise modeling was performed to detect regions with significantly different mechanical properties between each group. Mechanical signatures were summarized using pattern analysis and were used as features to train classification models and predict shunt outcomes for 2 sets of feature spaces: a limited 2D feature space that included the most common features found in normal pressure hydrocephalus and an expanded 20-dimensional (20D) feature space that included features from all 4 morphologic subgroups. RESULTS: Both the 2D and 20D classifiers performed significantly better than chance for predicting clinical outcomes with estimated areas under the receiver operating characteristic curve of 0.66 and 0.77, respectively (P < .05, permutation test). The 20D classifier significantly improved the diagnostic OR and positive predictive value compared with the 2D classifier (P < .05, permutation test). CONCLUSIONS: MR elastography provides further insight into mechanical alterations in the normal pressure hydrocephalus brain and is a promising, noninvasive method for predicting surgical outcomes in patients with normal pressure hydrocephalus.

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.

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.

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.

Impact of tumor markers on diagnosis, treatment and prognosis in CNS germ cell tumors: correlations with clinical practice and histopathology.

Tumor markers in CNS germ cell tumors (GCTs) include human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP), which have significant diagnostic implications, as elevation of either one leads to clinical diagnosis of non-germinomatous GCTs without histopathological confirmation, justifying intensified chemotherapy and irradiation. The current study, based on an international cohort of histopathologically verified GCTs that underwent biopsy (n = 85) or resection (n = 76), sought to better define the clinical role and prognostic significance of tumor markers from serum and CSF in this challenging patient population. We found that HCG was elevated only in cases with a germinoma or choriocarcinoma component, and there existed a clear cut-off HCG value between the two. AFP was often elevated in GCTs without a yolk sac tumor component, especially immature teratoma. HCG was elevated only in CSF in 3-of-52 cases, and AFP was elevated only in serum in 7-of-49 cases, emphasizing the potential utilization of both serum and CSF studies. Immature teratoma demonstrated unfavorable prognosis independent of tumor marker status, with 56% 5-year overall survival; however, co-existent germinoma components indicated a more favorable prognosis. Taken together, the study findings emphasize the importance for routine assessment and guarded interpretation of tumor markers in CNS GCTs.

Anatomical Step-by-Step Dissection of Complex Skull Base Approaches for Trainees: Surgical Anatomy of the Far Lateral Approach.

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.

Predictive Value of K i -67 Index in Evaluating Sporadic Vestibular Schwannoma Recurrence: Systematic Review and Meta-analysis.

Introduction K i -67 is often used as a proliferation index to evaluate how aggressive a tumor is and its likelihood of recurrence. Vestibular schwannomas (VS) are a unique benign pathology that lends itself well to evaluation with K i -67 as a potential marker for disease recurrence or progression following surgical resection. Methods All English language studies of VSs and K i -67 indices were screened. Studies were considered eligible for inclusion if they reported series of VSs undergoing primary resection without prior irradiation, with outcomes including both recurrence/progression and K i -67 for individual patients. For published studies reporting pooled K i -67 index data without detailed by-patient values, we contacted the authors to request data sharing for the current meta-analysis. Studies reporting a relationship between K i -67 index and clinical outcomes in VS for which detailed patients' outcomes or K i -67 indices could not be obtained were incorporated into the descriptive analysis, but excluded from the formal (i.e., quantitative) meta-analysis. Results A systematic review identified 104 candidate citations of which 12 met inclusion criteria. Six of these studies had accessible patient-specific data. Individual patient data were collected from these studies for calculation of discrete study effect sizes, pooling via random-effects modeling with restricted maximum likelihood, and meta-analysis. The standardized mean difference in K i -67 indices between those with and without recurrence was calculated as 0.79% (95% confidence interval [CI]: 0.28-1.30; p = 0.0026). Conclusion K i -67 index may be higher in VSs that demonstrate recurrence/progression following surgical resection. This may represent a promising means of evaluating tumor recurrence and potential need for early adjuvant therapy for VSs.

C1 lateral mass screw insertion using cannulated, navigated screws: preliminary results of a novel technique.

PURPOSE: The upper cervical spine region is densely populated by neural and vascular structures impeding the approach for fusion surgery. Technological advancement simplify the approach to C1-C2 fusion, thus reduce risks. The current paper purpose is to describe initial experience with a novel technique modification for C1 lateral screw insertion that incorporates cannulated-navigated screw system with intra-operative 3D imaging. METHODS: A single-center single surgeon database was reviewed to identify all patients who underwent placement of C1 lateral mass screw insertion using the novel technique modification described below, on 2020. This cohort was retrospectively analyzed and compared with a cohort of patients who were operated on by the same surgeon with non-cannulated, navigated screws with intra-operative 3D imaging (O-arm, Medtronic, USA) between 2011 and 2019. Following navigated starting hole and drilling of the C1 lateral mass, a blunt guide-wire is used to palpate the hole and cannulated screw is advanced to the correct position over the wire. After initial purchase, a navigated screw driver is used for final screw depth position. RESULTS: Twelve C1 lateral mass screws were inserted in six patients using this novel cannulated-navigated screw placement technique and compared to 24 patients operated using navigated non-cannulated screws. Minimal Estimated Blood Loss (EBL) was recorded in five of six cases undergoing the novel cannulated navigated placement of C1 lateral mass screws. Comparison to non-cannulated cohort demonstrated an EBL of 83CC vs. 354CC (Not significant). Mean surgery time was 97min and 118min for the cannulated-navigated and navigated only procedures (p = 0.03, statistically significant) respectively. In the current cohort, all screws were rated in optimal position and no repositioning procedures were performed. CONCLUSION: The new method presented allows for faster and possibly safer and more accurate C1 lateral mass screw insertion.

Post-laminectomy Dorsal Cord Migration Resulting in Immediate Neurologic Deterioration during Ventral Meningioma Resection: Proposed Mechanism of Injury and Prevention Technique.

BACKGROUND: Ventral thoracic meningiomas may pose a technical challenge owing to a limited surgical corridor and the presence of long-standing ventral cord compression. Unopposed dorsal spinal cord migration may occur following a laminectomy resulting in immediate neurologic injury. We discuss the possible mechanism underlying such a phenomenon, suggesting alternative approach to prevent neurologic injury. METHODS: Two patients operated on for ventral thoracic meningioma and sustained neurologic compromise were retrospectively evaluated. Image editing software was used for 3D modeling to simulate the possible underlying mechanism of injury. Cases where ventral thoracic meningiomas were approached via unilateral hemilaminectomy, performed in 2020, were retrospectively analyzed and compared with the laminectomy approach cohort. RESULTS: Two patients sustained postoperative neurologic function decline following resection of ventral thoracic meningioma via the laminectomy approach. Both exhibited permanent abolishment of transcranial motor evoked potentials (MEPs) following laminectomy. Based on the extrapolated 3D models for these two cases, dorsal cord migration was postulated as the cause for the acute neurologic compromise. CONCLUSION: Laminectomy for resection of thoracic ventral meningioma may lead in some cases to dorsal cord migration resulting in grave neurologic deterioration. Unilateral approach to these tumors restricts the dorsal migration and may mitigate neurologic outcomes.

Salvage radiosurgery following subtotal resection of vestibular schwannomas: does timing influence tumor control?

OBJECTIVE: The goal of microsurgical resection of vestibular schwannoma (VS) is gross-total resection (GTR) to provide oncological cure. However, a popular strategy is to halt the resection if the surgical team feels the risk of cranial nerve injury is imminent, achieving a maximally safe subtotal resection (STR) instead. The tumor remnant can then be treated with stereotactic radiosurgery (SRS) once the patient has recovered from the immediate postoperative period, or it can be followed with serial imaging and treated with SRS in a delayed fashion if residual tumor growth is seen. In this study, the authors evaluated the efficacy of this multimodality approach, particularly the influence of timing and dose of SRS on radiological tumor control, need for salvage treatment, and cranial nerve function. METHODS: VS patients treated with initial microsurgery and subsequent radiosurgery were retrospectively included from two tertiary treatment centers and dichotomized depending on whether SRS was given upfront (defined as before 12 months) or later. Radiological tumor control was defined as less than 20% tumor volume expansion and oncological tumor control as an absence of salvage treatment. Facial and cochlear nerve functions were assessed after surgery, at the time of SRS, and at last follow-up. Finally, a systematic literature review was conducted according to PRISMA guidelines. RESULTS: A total of 110 VS patients underwent SRS following microsurgical resection, with a mean preradiosurgical tumor volume of 2.2 cm3 (SD 2.5 cm3) and mean post-SRS follow-up time of 5.8 years (SD 4.1 years). The overall radiological tumor control and oncological tumor control were 77.3% and 90.9%, respectively. Thirty-five patients (31.8%) received upfront SRS, while 75 patients (68.2%) were observed for a minimum of 12 months prior to SRS. The timing of SRS did not influence the radiological tumor control (p = 0.869), the oncological tumor control (p = 0.560), or facial nerve (p = 0.413) or cochlear nerve (p = 0.954) function. An escalated marginal dose (> 12 Gy) was associated with greater tumor shrinkage (p = 0.020) and superior radiological tumor control (p = 0.020), but it did not influence the risk of salvage treatment (p = 0.904) or facial (p = 0.351) or cochlear (p = 0.601) nerve deterioration. CONCLUSIONS: Delayed SRS after close observation of residuals following STR is a safe alternative to upfront SRS regarding tumor control and cranial nerve preservation in selected patients.

Three-Dimensional Modeling for Augmented and Virtual Reality-Based Posterior Fossa Approach Selection Training: Technical Overview of Novel Open-Source Materials.

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.

Presentation, imaging, patterns of care, growth, and outcome in sporadic and von Hippel-Lindau-associated central nervous system hemangioblastomas.

OBJECT: Hemangioblastoma is a relatively rare neoplasm occurring mostly in the cerebellum that may arise sporadically or in the context of von Hippel-Lindau (VHL) syndrome. Presentation, imaging, natural history, surgical patterns of care, and outcomes are incompletely defined for this uncommon lesion. We reviewed our large institutional series to help clarify these issues. METHODS: Retrospective analysis of consecutive, neurosurgically managed CNS hemangioblastomas at Mayo Clinic, 1988-2018. RESULTS: Two hundred and eighty five hemangioblastomas were treated in 184 unique patients (115 sporadic, 69 VHL). Compared to sporadic patients, VHL patients were younger (36.7 vs 51.7 years; p < 0.0001), were treated while asymptomatic more commonly (47.3 vs 4.2%; p < 0.0001), had smaller lesions (6.6 vs 13.9 mL; p < 0.0001), and harbored lesions with associated cysts less frequently (51.0 vs 75.0%; p = 0.0002). Macrocystic tumor architecture was associated with larger lesion size and greater symptom severity. Solid lesions later formed cysts at a median 130 months. Growth in both total volume and solid component accelerated after cyst formation (10.6 and 6.0 times median rate prior to cyst emergence). VHL patients died at a younger age (47.9 vs 74.5, p = 0.0017) and were more likely to die of direct disease sequelae. Though treatment-free survival time was significantly longer in sporadic cases, a substantial fraction (> 40%) developed tumor recurrence/progression requiring additional treatment. CONCLUSIONS: Hemangioblastoma presentation varies with etiology and clinical course is more complicated in VHL cases. Nodular lesions often develop cysts over time which is associated with accelerated tumor growth. Sporadic cases have a previously unappreciated but substantial risk of late recurrence/progression requiring treatment.

Cerebrovascular Complications of Vestibular Schwannoma Surgery.

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.

3D Printing for Complex Cranial Surgery Education: Technical Overview and Preliminary Validation Study.

Background 3D printing-also known as additive manufacturing-has a wide range of applications. Reproduction of low-cost, high-fidelity, disease- or patient-specific models presents a key developmental area in simulation and education research for complex cranial surgery. Methods Using cadaveric dissections as source materials, skull base models were created, printed, and tested for educational value in teaching complex cranial approaches. In this pilot study, assessments were made on the value of 3D printed models demonstrating the retrosigmoid and posterior petrosectomy approaches. Models were assessed and tested in a small cohort of neurosurgery resident subjects ( n = 3) using a series of 10 radiographic and 2 printed case examples, with efficacy determined via agreement survey and approach selection accuracy. Results All subjects indicated agreement or strong agreement for all study endpoints that 3D printed models provided significant improvements in understanding of neuroanatomic relationships and principles of approach selection, as compared to 2D dissections or patient cross-sectional imaging alone. Models were not superior to in-person hands-on teaching. Mean approach selection accuracy was 90% (±13%) for 10 imaging-based cases, or 92% (±7%) overall. Trainees strongly agreed that approach decision-making was enhanced by adjunctive use of 3D models for both radiographic and printed cases. Conclusion 3D printed models incorporating skull base approaches and/or pathologies provide a compelling addition to the complex cranial education armamentarium. Based on our preliminary analysis, 3D printed models offer substantial potential for pedagogical value as dissection guides, adjuncts to preoperative study and case preparation, or tools for approach selection training and evaluation.

Anatomical Step-by-Step Dissection of Complex Skull Base Approaches for Trainees: Surgical Anatomy of the Middle Fossa Approaches and Anterior Petrosectomy, Surgical Principles, and Illustrative Cases.

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.

The Effect of Prescription Isodose Variation on Tumor Control and Toxicities in Stereotactic Radiosurgery for Sporadic Vestibular Schwannoma: Propensity Score-Matched Case-Control Study.

Objective Vestibular schwannoma (VS) treated with Gamma Knife stereotactic radiosurgery (SRS) was typically performed at 50% isodose line (IDL50); however, the impact of IDL variation on outcomes is poorly understood. This study aimed to compare tumor control (TC) and toxicities between treatment at 40% (IDL40) and 50% (IDL50). Methods Sporadic/unilateral VS patients treated with SRS dose 12 to 14 Gy and prescription isodose volume ≤10cm 3 were included. Propensity score matching was applied to IDL40 cohort to generate an IDL50 companion cohort, adjusting for age and prescription isodose volume. After exclusion of patients with follow-up <24 months, there were 30 and 28 patients in IDL40 and IDL50 cohorts, respectively. Results Median follow-up time was 96 months (24-225 months). Actuarial and radiographic TC rates were 91.8% and clinical TC was 96.2% both at 5 and 10 years. TC was higher in IDL40 cohort but not significant (96.4 vs. 86.7%; p = 0.243). Hearing preservation (HP) rates were 71.9 and 39.2% at 5- and 10-year intervals, with significantly higher rates of HP noted in IDL40 cohort (83.3 vs. 57.1% at 5-year interval; 62.5 vs. 11.4% at 10-year interval; p = 0.017). Permanent facial neuropathy occurred in two patients, both from the IDL50 cohort (3.5%). Rates of post-SRS steroid treatment or shunt placement for hydrocephalus were slightly higher in IDL50 patients (6.9 vs. 17.9%; p = 0.208 and 3.3 vs. 7.1%; p = 0.532). Conclusion For treatment of VS with SRS, dose prescription at IDL40 or IDL50 provides excellent long-term TC and toxicity profiles. IDL40 may be associated with improved long-term HP.

Novel Focal Therapeutic Hypothermia Device for Treatment of Acute Neurologic Injury: Large Animal Safety and Efficacy Trial.

Objective Therapeutic hypothermia is a potentially powerful and controversial clinical tool for neuroprotection following acute neurologic pathology, particularly vascular injury. Indeed, therapeutic hypothermia remains a standard of care for postcardiac arrest ischemia and acute neonatal hypoxic-ischemic encephalopathy, improving both survival and outcomes. Although therapeutic hypothermia remains promising for cellular and systems-based neuronal protection in other neurologic injury states, the systemic side effects have limited clinical utility, confounded analysis of potential neurologic benefits, and precluded the completion of meaningful clinical trials. Methods To address such limitations, we developed and tested a novel, minimally invasive, neurocritical care device that employs continuous circulation of cold saline through the pharyngeal region to deliver focal cerebrovascular cooling. We conducted a preclinical safety and efficacy trial in six adult porcine animals to assess the validity and functionality of the NeuroSave device, and assess cooling potential following middle cerebral artery occlusion ( n = 2). Results NeuroSave consistently lowered brain parenchymal temperature by a median of 9°C relative to core temperature within 60 minutes of initiation, including in ischemic cerebral parenchyma. The core body temperature experienced a maximal reduction of 2°C, or 5% of body temperature, with no associated adverse effects identified. Conclusion The present study uses a large animal preclinical model to demonstrate the safety and efficacy of a novel, noninvasive device for the induction of robust and systemically safe hypothermia within the brain.

Roles of Tumor Markers in Central Nervous System Germ Cell Tumors Revisited with Histopathology-Proven Cases in a Large International Cohort.

The central nervous system germ cell tumor (CNS GCT) is a rare and incompletely understood disease. A major outstanding question in the 2015 consensus document for CNS GCT management was the utility and interpretation of the tumor markers human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) in the diagnosis of malignant non-germinomatous GCTs (hereafter NGGCTs) prior to treatment. In the current study, we assembled two geographically and ethnically different clinical cohorts from the Mayo Clinic (1988-2017) and the intracranial GCT Genome Analysis Consortium (iGCT Consortium) in Japan to address this question. Patients with both histopathological diagnosis and tumor markers available were eligible for inclusion (n = 162). Biopsy and surgical resection were performed in 85 and 77 cases, respectively. Among 77 resections, 35 demonstrated positivity for HCG, AFP, or both (45%). Seventeen of the marker-positive cases had no malignant non-germinomatous component identified on histopathology, but they were composed strictly of germinoma, teratoma, or both (49%). One embryonal carcinoma was the only marker-negative NGGCT in the study sample. Among 85 biopsies, 18 were marker positive (21%). Seven of these patients had no malignant non-germinomatous component on histopathology, suggesting the potential limitations of limited tissue sample volumes. Neither histopathological diagnosis nor tumor markers alone reliably diagnose NGGCTs due to the secretion of HCG and AFP by germinomas and teratomas. Treatment planning should incorporate integrated histopathological and laboratory-based diagnosis to optimize diagnostic and treatment strategies for this unusual and histologically heterogeneous tumor.

A clinical primer for the glymphatic system.

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.