Search

Background: The surgical management of aneurysms involving the proximal third of the anterior inferior cerebellar artery (AICA) usually necessitates complex and invasive approaches, thus posing major challenges. We aimed to investigate the infratentorial presigmoid retrolabyrinthine suprameatal approach (PRSA) as a surgical corridor for premeatal AICA aneurysms., Methods: We performed 10 PRSA dissections in five cadaveric heads. Twelve morphometric parameters were measured, analyzed, and categorized into pre-procedural, intra-procedural, and additional parameters. The typical anatomic-radiological characteristics and variations were evaluated, and the related anatomical and radiological parameters were analyzed to predict surgical accessibility., Results: Preoperative anatomic-radiological parameters provide valuable information to select patients with favorable anatomy that may offer appropriate surgical accessibility to the premeatal AICA through a PRSA corridor. The position of the basilar artery from the midline determines the degree of accessibility to the origin of AICA through the infratentorial PRSA. The PRSA for targeting proximal AICA aneurysms was also compared to other surgical approaches based on the available current literature., Conclusion: Premeatal AICA aneurysms can be accessed and clipped through the infratentorial PRSA corridor. This would allow surgeons to avoid the sacrifice of hearing and balance as compared to other available invasive alternative approaches. The selection of the appropriate patients should be based on the individualized preoperative radiological characteristics for both the vascular and bony anatomy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Purpose: Posterior circulation cerebral bypasses often show higher risks and lower patency. Only few reports discussed occipital artery (OA)-vertebral artery (VA) bypasses. We present our illustrative cases to address current gaps in the literature on OA-VA bypass., Methods: A single-center retrospective review was conducted to include all institutional cases of OA-VA bypass, discussing the technique and outcomes., Results: Four institutional cases undergoing a total of 5 bypasses were evaluated, including 3 males and 1 female, with median age of 65 years (range, 62-73). All patients had vertebrobasilar insufficiency (VBI) with recurrent strokes/TIAs due to intracranial atherosclerosis, leading to unilateral VA stenosis with contralateral occlusion (1, 25%), bilateral VA stenosis (1, 25%) or occlusion (1, 25%). Medical management included aspirin for all cases (100%), with clopidogrel in 3 (75%). Surgery was performed through a far lateral approach, connecting the OA to the VA-3 segment, with no inter-positional graft. One patient underwent contralateral OA-VA bypass 6 months after the prior surgery due to worsening of the contralateral VA stenosis. Bypass patency was confirmed in all cases with post-operative angiography. All patients had clinical improvement, with one case of wound dehiscence managed conservatively. All patients were alive at last follow-up (median 7.0 months; range: 1.5-18)., Conclusion: OA-VA bypass is a challenging yet effective strategy in selected patients with VBI. Current literature lacks unique definitions of surgical indications and techniques, which we addressed in our series. Surgical education should focus on expanding the microsurgery anatomy knowledge., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Supratentorial craniotomy represents the upper part of the combined trans-tentorial or the supra-infratentorial presigmoid approach. In this study, we provide qualitative and quantitative analyses for the supratentorial extension of the presigmoid retrolabyrinthine suprameatal approach (PRSA)., Methods: The infratentorial PRSA followed by the supratentorial extension craniotomy with dividing and removal of the tentorial strip were performed on both sides of 5 injected human cadaver heads (n = 10 sides). Quantitative analysis was performed for the surface area gained (surgical accessibility) by adding the supratentorial craniotomy. Qualitative analysis was performed for the parts of the brainstem, cranial nerves, and vascular structures that became accessible by adding the supratentorial craniotomy. The anatomical obstacles encountered in the added operative corridor were analyzed., Results: The supratentorial extension of PRSA provides an increase in surgical accessibility of 102.65% as compared to the PRSA standalone. The mean surface area of the exposed brainstem is 197.98 (standard deviation: 76.222) and 401.209 (standard deviation: 123.96) for the infratentorial and the combined supra-infratentorial presigmoid approach, respectively. Exposure for parts of III, IV, and V cranial nerves is added after the extension, and the surface area of the outer craniotomy defect has increased by 60.32%. Parts of the basilar, anterior inferior cerebellar, and superior cerebellar arteries are accessible after the supratentorial extension., Conclusions: The supratentorial extension of PRSA allows access to the supra-trigeminal area of the pons and the lower part of the midbrain. Considering this surgical accessibility and exposure significantly assists in planning such complex approaches while targeting central skull base lesions., (Published by Elsevier Inc.)

Purpose: High-grade gliomas (HGG) carry a poor prognosis, with glioblastoma accounting for almost 50% of primary brain malignancies in the elderly. Unfortunately, despite the use of multiple treatment modalities, the prognosis remains poor in this population. Our preclinical studies suggest that the presence of aromatase expression, encoded by CYP19A1, is significantly upregulated in HGGs. Remarkably, we find that letrozole (LTZ), an FDA-approved aromatase inhibitor, has marked activity against HGGs., Patients and Methods: We conducted a phase 0/I single-center clinical trial (NCT03122197) to assess the tumoral availability, pharmacokinetics (PK), safety, and tolerability of LTZ in recurrent patients with HGG. Planned dose cohorts included 2.5, 5, 10, 12.5, 15, 17.5, and 20 mg of LTZ administered daily pre- and postsurgery or biopsy. Tumor samples were assayed for LTZ content and relevant biomarkers. The recommended phase 2 dose (R2PD) was determined as the dose that resulted in predicted steady-state tumoral extracellular fluid (ECF; Css,ecf) >2 μmol/L and did not result in ≥33% dose-limiting adverse events (AE) assessed using CTCAE v5.0., Results: Twenty-one patients were enrolled. Common LTZ-related AEs included fatigue, nausea, musculoskeletal, anxiety, and dysphoric mood. No DLTs were observed. The 15 mg dose achieved a Css,ecf of 3.6 ± 0.59 μmol/L. LTZ caused dose-dependent inhibition of estradiol synthesis and modulated DNA damage pathways in tumor tissues as evident using RNA-sequencing analysis., Conclusions: On the basis of safety, brain tumoral PK, and mechanistic data, 15 mg daily is identified as the RP2D for future trials., (©2024 American Association for Cancer Research.)

Background: Transcortical approaches, encompassing various surgical corridors, have been employed to treat an array of intraparenchymal or intraventricular brain pathologies, including tumors, vascular malformations, infections, intracerebral hematomas, and epileptic surgery. Designing cortical incisions relies on the lesion location and characteristics, knowledge of eloquent functional anatomy, and advanced imaging such as tractography. Despite their widespread use in neurosurgery, there is a noticeable lack of systematic studies examining their common lobe access points, associated complications, and prevalent pathologies. This scoping review assesses current evidence to guide the selection of transcortical approaches for treating a variety of intracranial pathologies., Methods: A scoping review was conducted using the PRISMA-ScR guidelines, searching PubMed, EMBASE, Scopus, and Web of Science. Studies were included if ≥5 patients operated on using transcortical approaches, with reported data on clinical features, treatments, and outcomes. Data analysis and synthesis were performed., Results: A total of 50 articles encompassing 2604 patients were included in the study. The most common primary pathology was brain tumors (60.6%), particularly gliomas (87.4%). The transcortical-transtemporal approach was the most frequently identified cortical approach (70.48%), and the temporal lobe was the most accessed brain lobe (55.68%). The postoperative course outcomes were reported as good (55.52%), poor (28.38%), and death (14.62%)., Conclusion: Transcortical approaches are crucial techniques for managing a wide range of intracranial lesions, with the transcortical-transtemporal approach being the most common. According to the current literature, the selective choice of cortical incision and surgical corridor based on the lesion's pathology and anatomic-functional location correlates with acceptable functional outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

The divergent synthesis of two indane polyketides of the indidene family, namely (±)-indidene A (11 steps, 1.7 %) and (+)-indidene C (13 steps, 1.3 %), is reported. The synthesis of the trans-configured common indane intermediate was enabled by palladium(0)-catalyzed methylene C(sp 3 )-H arylation, which was performed in both racemic and enantioselective (e.r. 99 : 1) modes. Further elaboration of this common intermediate by nickel-catalyzed dehydrogenative coupling allowed the rapid installation of the aroyl moiety of (±)-indidene A. In parallel, the biphenyl system of (±)- and (+)-indidene C was constructed by Suzuki-Miyaura coupling. These investigations led us to revise the structures of indidenes B and C., (© 2023 Wiley-VCH GmbH.)

Background and Objectives: Access to the anterolateral pontine lesions can be achieved through the peritrigeminal and supratrigeminal safe entry zones using Kawase, retrosigmoid, or translabyrinthine approaches. However, these approaches entail shallow extensive dissection, tangential access, and compromise vestibulocochlear function. We aimed to investigate infratentorial presigmoid retrolabyrinthine approach to access pontine lesions through the peritrigeminal zone., Methods: We performed 10 presigmoid retrolabyrinthine suprameatal approach dissections in 5 cadaveric heads. Anatomic-radiological characteristics and variations were evaluated. Six morphometric parameters were measured and analyzed to predict surgical accessibility., Results: The pontine infratrigeminal area was accessible in all patients. The mean exposed area of the anterolateral pontine surface was 98.95 cm 2 (±38.11 cm 2 ). The mean length of the exposed trigeminal nerve was 7.9 cm (±2.9 cm). Preoperative anatomic-radiological parameters may allow to select patients with favorable anatomy that offers appropriate surgical accessibility to the anterior pontine cavernoma through a presigmoid retrolabyrinthine corridor., Conclusion: Anterolateral pontine lesions can be accessed through a minimally invasive infratentorial presigmoid retrolabyrinthine approach by targeting the infratrigeminal safe entry zone. Further clinical studies should be conducted to evaluate the viability of this technique for treating these complex pathologies in real clinical settings., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background and Purpose: Emerging data suggest immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) or radiotherapy (SRT) may work synergistically, potentially increasing both efficacy and toxicity. This manuscript characterizes factors associated with intracranial control and radiation necrosis in this group., Materials and Methods: All patients had non-small cell lung cancer, renal cell carcinoma, or melanoma and were treated from 2013 to 2021 at two institutions with ICI and SRS/SRT. Univariate and multivariate analysis were used to analyze factors associated with local failure (LF) and grade 2+ (G2 + ) radiation necrosis., Results: There were 179 patients with 549 metastases. The median follow up from SRS/SRT was 14.7 months and the median tumor size was 7 mm (46 tumors ≥ 20 mm). Rates of LF and G2 + radiation necrosis per metastasis were 5.8% (32/549) and 6.9% (38/549), respectively. LF rates for ICI +/- 1 month from time of radiation versus not were 3% (8/264) and 8% (24/285) (p = 0.01), respectively. G2 + radiation necrosis rates for PD-L1 ≥ 50% versus < 50% were 17% (11/65) and 3% (5/203) (p=<0.001), respectively. PD-L1 ≥ 50% remained significantly associated with G2 + radiation necrosis on multivariate analysis (p = 0.03). Rates of intracranial failure were 54% (80/147) and 17% (4/23) (p = 0.001) for those without and with G2 + radiation necrosis, respectively., Conclusions: PD-L1 expression (≥50%) may be associated with higher rates of G2 + radiation necrosis, and there may be improved intracranial control following the development of radiation necrosis. Administration of ICIs with SRS/SRT is overall safe, and there may be some local control benefit to delivering these concurrently., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Exclusive endoscopic (EETTA) and expanded (ExpTTA) transcanal transpromontorial approaches have shown promising results for treating internal auditory canal (IAC) lesions. We reviewed the literature to answer the question: "Do EETTA and ExpTTA achieve high rates of complete resection and low rates of complications in treating patients with IAC pathologies?", Data Sources: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched., Review Methods: Studies reporting EETTA/ExpTTA for IAC pathologies were included. Indications and techniques were discussed and meta-analyzed rates of outcomes and complications were obtained with random-effect model meta-analyses., Results: We included 16 studies comprising 173 patients, all with non-serviceable hearing. Baseline FN function was mostly House-Brackmann-I (96.5%; 95% CI: 94.9-98.1%). Most lesions were vestibular/cochlear schwannomas (98.3%; 95% CI: 96.7-99.8%) of Koos-I (45.9%; 95% CI: 41.3-50.3%) or II (47.1%; 95% CI: 43-51.1%). EETTA was performed in 101 patients (58.4%; 95% CI: 52.4-64.3%) and ExpTTA in 72 (41.6%; 95% CI: 35.6-47.6%), achieving gross-total resection in all cases. Transient complications occurred in 30 patients (17.3%; 95% CI: 13.9-20.5%), with meta-analyzed rates of 9% (95% CI: 4-15%), comprising FN palsy with spontaneous resolution (10.4%; 95% CI: 7.7-13.1%). Persistent complications occurred in 34 patients (19.6%; 95% CI: 17.1-22.2%), with meta-analyzed rates of 12% (95% CI: 7-19%), comprising persistent FN palsy in 22 patients (12.7%; 95% CI: 10.2-15.2%). Mean follow-up was 16 months (range, 1-69; 95% CI: 14.7-17.4). Post-surgery FN function was stable in 131 patients (75.8%; 95% CI: 72.1-79.5%), worsened in 38 (21.9%; 95% CI: 18.8-25%), and improved in 4 (2.3%; 95% CI: 0.7-3.9%), with meta-analyzed rates of improved/stable response of 84% (95% CI: 76-90%)., Conclusion: Transpromontorial approaches offer newer routes for IAC surgery, but their restricted indications and unfavorable FN outcomes currently limit their use. Laryngoscope, 133:2856-2867, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

We report mechanistic studies on the reactivity of different α-substituted C(sp 3 )-H bonds, -CH n R (R = H, Me, CO 2 Me, CONMe 2 , OMe, and Ph, as well as the cyclopropyl and isopropyl derivatives -CH(CH 2 ) 2 and -CHMe 2 ) in the context of Pd 0 -catalyzed C(sp 3 )-H arylation. Primary kinetic isotope effects, k H / k D , were determined experimentally for R = H (3.2) and Me (3.5), and these, along with the determination of reaction orders and computational studies, indicate rate-limiting C-H activation for all substituents except when R = CO 2 Me. This last result was confirmed experimentally ( k H / k D ∼ 1). A reactivity scale for C(sp 3 )-H activation was then determined: C H 2 CO 2 Me > C H (CH 2 ) 2 ≥ C H 2 CONMe 2 > C H 3 ≫ C H 2 Ph > C H 2 Me > C H 2 OMe ≫ C H Me 2 . C-H activation involves AMLA/CMD transition states featuring intramolecular O → H-C H-bonding assisted by C-H → Pd agostic bonding. The "AMLA coefficient", χ, is introduced to quantify the energies associated with these interactions via natural bond orbital 2nd order perturbation theory analysis. Higher barriers correlate with lower χ values, which in turn signal a greater agostic interaction in the transition state. We believe that this reactivity scale and the underlying factors that determine this will be of use for future studies in transition-metal-catalyzed C(sp 3 )-H activation proceeding via the AMLA/CMD mechanism., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Delayed cerebral ischemia (DCI) may significantly worsen the functional status of patients with aneurysmal subarachnoid hemorrhage (aSAH). Several authors have designed predictive models for early identification of patients at risk of post-aSAH DCI. In this study, we externally validate an extreme gradient boosting (EGB) forecasting model for post-aSAH DCI prediction., Methods: A 9-year institutional retrospective review of patients with aSAH was performed. Patients were included if they underwent surgical or endovascular treatment and had available follow-up data. DCI was diagnosed as new-onset neurologic deficits at 4-12 days after aneurysm rupture, defined as worsening Glasgow Coma Scale score for ≥2 points, and new ischemic infarcts at imaging., Results: We collected 267 patients with aSAH. At admission, median Hunt-Hess score was 2 (range, 1-5), median Fisher score 3 (range, 1-4), and median modified Fisher score 3 (range, 1-4). One-hundred and forty-five patients underwent external ventricular drainage placement for hydrocephalus (54.3%). The ruptured aneurysms were treated with clipping (64%), coiling (34.8%), and stent-assisted coiling (1.1%). Fifty-eight patients (21.7%) were diagnosed with clinical DCI and 82 (30.7%) with asymptomatic imaging vasospasm. The EGB classifier correctly predicted 19 cases of DCI (7.1%) and 154 cases of no-DCI (57.7%), achieving sensitivity of 32.76% and specificity of 73.68%. The calculated F1 score and accuracy were 0.288% and 64.8%, respectively., Conclusions: We validated that the EGB model is a potential assistant tool to predict post-aSAH DCI in clinical practice, finding moderate-high specificity but low sensitivity. Future research should investigate the underlying pathophysiology of DCI to allow the development of high-performing forecasting models., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Aneurysm morphology has been correlated with rupture. Previous reports identified several morphologic indices that predict rupture status, but they measure only specific qualities of the morphology of an aneurysm in a semiquantitative fashion. Fractal analysis is a geometric technique whereby the overall complexity of a shape is quantified through the calculation of a fractal dimension (FD). By progressively altering the scale of measurement of a shape and determining the number of segments required to incorporate the entire shape, a noninteger value for the dimension of the shape is derived. We present a proof-of-concept study to calculate the FD of an aneurysm for a small cohort of patients with aneurysms in 2 specific locations to determine whether FD is associated with aneurysm rupture status., Methods: Twenty-nine aneurysms of the posterior communicating and middle cerebral arteries were segmented from computed tomography angiograms in 29 patients. FD was calculated using a standard box-counting algorithm extended for use with three-dimensional shapes. Nonsphericity index and undulation index (UI) were used to validate the data against previously reported parameters associated with rupture status., Results: Nineteen ruptured and 10 unruptured aneurysms were analyzed. Through logistic regression analysis, lower FD was found to be significantly associated with rupture status (P = 0.035; odds ratio, 0.64; 95% confidence interval, 0.42-0.97 per FD increment of 0.05)., Conclusions: In this proof-of-concept study, we present a novel approach to quantify the geometric complexity of intracranial aneurysms through FD. These data suggest an association between FD and patient-specific aneurysm rupture status., (Copyright © 2023. Published by Elsevier Inc.)

Green and sustainable access to chiral and achiral gold-IBiox complexes is reported. The gold complexes were synthesized using a simple, air-tolerant, weak base protocol carried out in a green solvent. Their catalytic activity was examined in the hydroamination of alkynes. The steric protection afforded the gold center by these ligands was quantified using the % V bur model and compared with the most commonly encountered NHCs.

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors. In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = 0.010) as per interim efficacy analysis. The ChemoID assay-guided group has a significantly lower risk of death (hazard ratio [HR] = 0.44; 95% CI, 0.24-0.81; p = 0.008). Results of this study offer a promising way to provide more affordable treatment for patients with rGBM in lower socioeconomic groups in the US and around the world., Competing Interests: Declaration of interests P.P.C. and J.V. report ownership of intellectual property rights on the CSC platform technology licensed to Cordgenics, LLC., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cerebrospinal fluid rhinorrhea after temporal bone surgery involves drainage from the Eustachian tube (ET) into the nasopharynx, causing significant patient morbidity. Variable anatomy of the ET accounts for failures of currently used ET obliteration techniques., Objective: To describe the surgical anatomy of the ET and examine possible techniques for ET closure through middle fossa (MF) and transmastoid approaches., Methods: We described the surgical anatomy of the ET from the MF and transmastoid approaches in 5 adult cadaveric heads, measuring morphometric and surgical anatomy parameters and establishing targets for definite ET obliteration., Results: The osseous ET measured an average of 19.53 mm (±1.56 mm), with a mean diameter of 2.24 mm (±0.29 mm). The shortest distance between the greater superficial petrosal nerve and the ET junction was 6.61 mm (±0.61 mm). Shortest distances between the ET junction and the foramen spinosum and posterior border of the foramen ovale were 1.09 mm (±0.24 mm) and 2.03 mm (±0.30 mm), respectively. Closure of the cartilaginous ET may be performed by folding it in on itself, securing it by packing, suturing, or surgical clip ligation., Conclusion: Definite obliteration of the cartilaginous ET appears feasible and the most definite approach to eliminate egress of cerebrospinal fluid to the nasopharynx using the MF approach. This technique may be used as an adjunct to skull base procedures where ET closure is planned., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: Rathke cleft cysts (RCCs) are common benign skull-base lesions arising from embryologic remnants of Rathke pouch. Though frequently asymptomatic, RCCs can become symptomatic because of compression of adjacent neural structures. Transcranial and neuroendoscopic surgical treatments have been described for symptomatic RCCs, but recurrence rates remain as high as 30%. Bioabsorbable steroid-eluting (BASE) stents significantly decrease adhesions and recurrent ostia obstruction after endoscopic sinus surgery. We sought to use BASE stents to aid marsupialization of symptomatic RCCs., Objective: To present long-term results of our initial experience with endoscopic-endonasal fenestration and placement of BASE stents for RCCs., Methods: Patients undergoing neuroendoscopic transsphenoidal fenestration of RCCs with BASE stent placement were identified and their medical records retrospectively reviewed., Results: Four patients underwent neuroendoscopic transsphenoidal fenestration and BASE stent placement from March 2016 to April 2018 for symptomatic RCCs. After the cyst contents were evacuated, a BASE stent was deployed in the cyst fenestration to prevent cyst wall regrowth or closure and facilitate marsupialization to the sphenoid sinus. No perioperative complications were encountered, and all patients reported symptom resolution by 2 weeks postoperatively. Postoperative endoscopic evaluation demonstrated epithelization of the cyst wall opening and patent marsupialization into the sphenoid sinus in all cases. After a mean follow-up of 56 ± 12 months, all patients remained asymptomatic with baseline visual function and no radiographic evidence of recurrence., Conclusion: Bioabsorbable steroid-eluting stent placement is a safe, facile, viable augmentation of neuroendoscopic technique for symptomatic RCCs with the potential to reduce long-term recurrence rates., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Objectives  This study seeks to comprehensively analyze the impact of smoking history on outcomes after endoscopic transsphenoidal hypophysectomy (TSH) for pituitary adenoma. Design  This was a retrospective study. Setting  This study was done at the tertiary care center. Participants  Three hundred and ninety-eight adult patients undergoing TSH for a pituitary adenoma. Main Outcome Measures  Clinical and tumor characteristics and operative factors were collected. Patients were categorized as never, former, or active smokers, and the pack-years of smoking history was collected. Years since cessation of smoking was obtained for former smokers. Specific outcomes included postoperative cerebrospinal fluid (CSF) leak, length of hospitalization, 30-day return to the operating room, and 30-day readmission. Smoking history details were comprehensively analyzed for association with outcomes. Results  Any history of smoking tobacco was associated with return to the operating room (odds ratio [OR] = 2.67, 95% confidence interval [CI]: 1.05-6.76, p  = 0.039), which was for persistent CSF leak in 58.3%. Among patients with postoperative CSF leak, any history of smoking was associated with need for return to the operating room to repair the CSF leak (OR = 5.25, 95% CI: 1.07-25.79, p  = 0.041). Pack-years of smoking was positively associated with a return to the operating room (OR = 1.03, 95% CI: 1.01-1.06, p  = 0.048). In all multivariable models, all negative outcomes were significantly associated with the covariate: occurrence of intraoperative CSF leak. Conclusion  This is the first study to show smoking may have a negative impact on healing of CSF leak repairs after TSH, requiring a return to the operating room. This effect appears to be dose dependent on the smoking history. Secondarily, intraoperative CSF leak as covariate in multivariable models was significantly associated with all negative outcomes., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objective: The "presigmoid corridor" covers a spectrum of approaches using the petrous temporal bone either as a target in treating intracanalicular lesions or as a route to access the internal auditory canal (IAC), jugular foramen, or brainstem. Complex presigmoid approaches have been continuously developed and refined over the years, leading to great heterogeneity in their definitions and descriptions. Owing to the common use of the presigmoid corridor in lateral skull base surgery, a simple anatomy-based and self-explanatory classification is needed to delineate the operative perspective of the different variants of the presigmoid route. Herein, the authors conducted a scoping review of the literature with the aim of proposing a classification system for presigmoid approaches., Methods: The PubMed, EMBASE, Scopus, and Web of Science databases were searched from inception to December 9, 2022, following the PRISMA Extension for Scoping Reviews guidelines to include clinical studies reporting the use of "stand-alone" presigmoid approaches. Findings were summarized based on the anatomical corridor, trajectory, and target lesions to classify the different variants of the presigmoid approach., Results: Ninety-nine clinical studies were included for analysis, and the most common target lesions were vestibular schwannomas (60/99, 60.6%) and petroclival meningiomas (12/99, 12.1%). All approaches had a common entry pathway (i.e., mastoidectomy) but were differentiated into two main categories based on their relationship to the labyrinth: translabyrinthine or anterior corridor (80/99, 80.8%) and retrolabyrinthine or posterior corridor (20/99, 20.2%). The anterior corridor comprised 5 variations based on the extent of bone resection: 1) partial translabyrinthine (5/99, 5.1%), 2) transcrusal (2/99, 2.0%), 3) translabyrinthine proper (61/99, 61.6%), 4) transotic (5/99, 5.1%), and 5) transcochlear (17/99, 17.2%). The posterior corridor consisted of 4 variations based on the target area and trajectory in relation to the IAC: 6) retrolabyrinthine inframeatal (6/99, 6.1%), 7) retrolabyrinthine transmeatal (19/99, 19.2%), 8) retrolabyrinthine suprameatal (1/99, 1.0%), and 9) retrolabyrinthine trans-Trautman's triangle (2/99, 2.0%)., Conclusions: Presigmoid approaches are becoming increasingly complex with the expansion of minimally invasive techniques. Descriptions of these approaches using the existing nomenclature can be imprecise or confusing. Therefore, the authors propose a comprehensive classification based on the operative anatomy that unequivocally describes presigmoid approaches simply, precisely, and efficiently.

Background: Color-labeling injections of cadaveric heads have revolutionized education and teaching of neurovascular anatomy. Silicone-based and latex-based coloring techniques are currently used, but limitations exist because of the viscosity of solutions used., Objective: To describe a novel "triple-injection method" for cadaveric cranial vasculature and perform qualitative and semiquantitative evaluations of colored solution penetration into the vasculature., Methods: After catheter preparation, vessel cannulation, and water irrigation of embalmed cadaveric heads, food coloring, gelatin, and silicone solutions were injected in sequential order into bilateral internal carotid and vertebral arteries (red-colored) and internal jugular veins (blue-colored). In total, 6 triple-injected embalmed cadaveric heads and 4 silicone-based "control" embalmed cadaveric heads were prepared. A qualitative analysis was performed to compare the vessel coloring of 6 triple-injected heads with that of 4 "control" heads. A semiquantitative evaluation was completed to appraise sizes of the smallest color-filled vessels., Results: Naked-eye and microscope evaluations of embalmed experimental and control cadaveric heads revealed higher intensity and more distal color-labeling following the "triple-injection method" compared with the silicone-based method in both the intracranial and extracranial vasculature. Microscope assessment of 1-mm-thick coronal slices of triple-injected brains demonstrated color-filling of distal vessels with minimum diameters of 119 μm for triple-injected heads and 773 μm for silicone-based injected heads., Conclusion: Our "triple-injection method" showed superior color-filling of small-sized vessels as compared with the silicone-based injection method, resulting in more distal penetration of smaller caliber vessels., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Surgical intervention for the treatment of intracerebral hemorrhage (ICH) has been limited by inadequate lysis of the target thrombus. Adjuvant transcranial ultrasound exposure is hypothesized to improve thrombolysis, expedite hematoma evacuation and improve clinical outcomes. A juvenile porcine intracerebral hemorrhage model was established by direct infusion of autologous blood into the porcine white matter. Thrombi were either not treated (sham) or treated with recombinant tissue plasminogen activator alone (rt-PA only) or in combination with pulsed transcranial 120-kHz ultrasound (sonothrombolysis). After treatment, pigs were euthanized, the heads frozen and sectioned and the thrombi extracted. D-Dimer and thrombus density assays were used to assess degree of lysis. Both porcine and human D-dimer assays tested did not have sufficient sensitivity to detect porcine D-dimer. Thrombi treated with rt-PA with or without 120-kHz ultrasound had a significantly lower density compared with sham-treated thrombi. No enhancement of rt-PA-mediated thrombolysis was noted with the addition of 120-kHz ultrasound (sonothrombolysis). The thrombus density assay revealed thrombolytic efficacy caused by rt-PA in an in vivo juvenile porcine model of intracerebral hemorrhage. Transcranial sonothrombolysis did not enhance rt-PA-induced thrombolysis, likely because of the lack of exogenous cavitation nuclei., Competing Interests: Conflict of interest disclosure The authors have no conflicts of interest to declare with respect to the current article., (Copyright © 2022. Published by Elsevier Inc.)

Background: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants., Methods: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H 2 O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control., Discussion: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019., (© 2022. The Author(s).)

Background: There is a paucity of data in the literature describing quantitative exposure of the ventral craniocervical junction through the endonasal corridor in a safe manner mindful of locoregional anatomy., Objective: To quantify ventromedial exposure of O-C1 and C1-2 articular structures after turning an inverted U-shaped nasopharyngeal flap (IUNF) and to obtain measurements assessing the distance of flap margins to adjacent neurovascular structures., Methods: In 8 cadaveric specimens, an IUNF was fashioned using a superior incision below the level of the pharyngeal tubercule of the clivus and lateral incisions in the approximate region of Rosenmuller fossae bilaterally. Measurements with calipers and/or neuronavigation software included flap dimensions, exposure of O-C1 and C1-2 articular structures, inferior reach of IUNF, and proximity of the internal carotid artery (ICA) and hypoglossal nerve to IUNF margins., Results: The IUNF facilitated exposure of an average of 9 mm of the medial surfaces of the right/left O-C1 joints without transgression of the carotid arteries or hypoglossal nerves. The C1-2 articulation could not be routinely accessed. The margins of the IUNF were not in close (<5 mm) proximity to the ICA in any of the 8 specimens. In 6 of 8 specimens, the dimensions of the IUNF were in close (<5 mm) horizontal or vertical proximity to the hypoglossal foramina., Conclusion: The IUNF provided safe and reliable access to the medial O-C1 articulation. Given the close proximity of the exocranial hypoglossal foramen, neuronavigation assistance and neuromonitoring with attention to the superolateral IUNF margin are recommended., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant embryonal tumor of the CNS, largely affecting pediatric patients, with exceedingly rare cases in adults at an estimated annual incidence of 1/1,000,000. We report a unique case of ATRT in a 43-year-old female patient who first presented with progressive focal headaches. Imaging revealed a sellar mass with suprasellar extensions, which was partially removed via a transsphenoidal resection. The tumor aggressively recurred just 1 month postoperatively. Her care team pursued a novel treatment plan by using a slightly modified COG ACNS 0332 regimen, which involved radiation, followed by 4 cycles of monthly chemotherapy including vincristine, cyclophosphamide, and cisplatin. Hematopoietic stem cells were collected between radiation and chemotherapy in the event that the patient required stem cell salvage therapy postadjuvant chemotherapy. The MRIs taken at 2 and 4 months postrecurrence indicated a substantial decrease in tumor volume, with corresponding clinical improvements to cranial nerve deficits. Given the scarcity of literature on adult cases of ATRT and the lack of a standard of care for these cases, discussing the efficacy of our patient's treatment plan may aid clinical decision making for adult ATRT cases., (© 2022 American Academy of Neurology.)

Objective: Examine the effects of a multi-disciplinary skull base conference (MDSBC) on the management of patients seen for skull base pathology in a neurotology clinic., Methods: Retrospective case review of patients who were seen in a neurotology clinic at a tertiary academic medical center for pathology of the lateral skull base and were discussed at an MDSBC between July 2019 and February 2020. Patient characteristics, nature of the skull base pathology, and pre- and post-MDSBC plan of care was categorized., Results: A total of 82 patients with pathology of the lateral skull base were discussed at a MDSBC during an 8-month study period. About 54 (65.9%) had a mass in the internal auditory canal and/or cerebellopontine angle while 28 (34.1%) had other pathology of the lateral skull base. Forty-nine (59.8%) were new patients and 33 (40.2%) were established. The management plan changed in 11 (13.4%, 7.4-22.6 95% CI) patients as a result of the skull base conference discussion. The planned management changed from some form of treatment to observation in 4 patients, and changed from observation to some form of treatment in 4 patients. For 3 patients who underwent surgery, the planned approach was altered., Conclusions: For a significant proportion of patients with pathology of the lateral skull base, the management plan changed as a result of discussion at an MDSBC. Although participants of a MDSBC would agree of its importance, it is unclear how an MDSBC affects patient outcomes.

Objective: Cerebral arteriovenous malformations (AVMs) typify the delicate balance cerebrovascular specialists face in weighing the treatment risk against the natural history of a pathologic lesion. The goal of our review was to provide an overview of the current evidence for the treatment of cerebral AVMs and describe a contemporary approach to developing a treatment strategy according to individual AVM characteristics., Methods: A review of the contemporary literature on the natural history and treatment of cerebral AVMs was completed through the PubMed and Google Scholar databases. The studies were reviewed for original advances in the characterization and treatment of cerebral AVMs., Results: The overall risk of hemorrhage for cerebral AVMs is 2%-4% per year. Individual AVM characteristics, including small size, exclusive deep venous drainage, deep or posterior fossa location, venous ectasia, and the presence of a flow-associated aneurysm, appear to confer a greater risk of presentation with rupture. A diverse array of modalities have been developed to achieve the goal of complete lesion obliteration, including microsurgery, endovascular therapy, and radiosurgery. Advances in treatment strategies and technology have continued to decrease the morbidity associated with lesion obliteration., Conclusions: Microsurgical or multimodal treatment strategies are often required to achieve complete obliteration; however, it remains critical that each treatment approach is individualized by the specific AVM characteristics., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The aim of this study was to determine the incidence of cochlear fibrosis after vestibular schwannoma (VS) resection via middle cranial fossa (MCF) approach., Design: A retrospective case review was conducted., Setting: The review was conducted in a tertiary care academic medical center., Participants: Patients who (1) underwent resection of VS via MCF approach between 2013 and 2018, (2) had complete pre- and post-audiometric testing, and (3) had clinical follow-up with magnetic resonance imaging (MRI) for at least 1 year after surgery were included., Main Outcome Measure(s): The main outcome of this study was cochlear fibrosis as assessed by MRI 1 year after surgery., Results: Fifty-one patients underwent VS resection via MCF technique during the study period. Of 31 patients with AAO-HNS class A or B preoperative hearing ability, 18 (58.0%) maintained class A, B, or C hearing postoperatively. Of 16 patients who lost hearing and had MRI 1 year after surgery, 11 (61.1%) had MRI evidence of fibrosis in at least some portion of the labyrinth and 4 (22.2%) showed evidence of cochlear fibrosis. Of 16 patients with preserved hearing and MRI 1 year after surgery, 4 (25%) had fibrosis in some portion of the labyrinth, with no fibrosis in the cochlea., Conclusions: In patients who lose hearing during VS resection with the MCF approach, there is usually MRI evidence of fibrosis in the labyrinth 1 year after surgery. However, there is also, but less commonly, fibrosis involving the cochlea. It is unclear if this will affect the ability to insert a cochlear implant electrode array., (© 2022 S. Karger AG, Basel.)

Objective  Endonasal dural suturing (EDS) has been reported to decrease the incidence of cerebrospinal fluid fistula. This technique requires handling of single-shaft instrumentation in the narrow endonasal corridor. It has been proposed that three-dimensional (3D) endoscopes were associated with improved depth perception. In this study, we sought to perform a comparison of two-dimensional (2D) versus 3D endoscopy by assessing surgical proficiency in a simulated model of EDS. Materials and Methods  Twenty-six participants subdivided into groups based on previous endoscopic experience were asked to pass barbed sutures through preset targets with either 2D (Storz Hopkins II) or 3D (Storz TIPCAM) endoscopes on 3D-printed simulation model. Surgical precision and procedural time were measured. All participants completed a Likert scale questionnaire. Results  Novice, intermediate, and expert groups took 11.0, 8.7, and 5.7 minutes with 2D endoscopy and 10.9, 9.0, and 7.6 minutes with 3D endoscopy, respectively. The average deviation for novice, intermediate, and expert groups (mm) was 5.5, 4.4, and 4.3 with 2D and 6.6, 4.6, and 3.0 with 3D, respectively. No significant difference in procedural time or accuracy was found in 2D versus 3D endoscopy. 2D endoscopic visualization was preferred by the majority of expert/intermediate participants, while 3D endoscopic visualization by the novice group. Conclusion  In this pilot study, there was no statistical difference in procedural time or accuracy when utilizing 2D versus 3D endoscopes. While it is possible that widespread familiarity with 2D endoscopic equipment has biased this study, preliminary analysis suggests that 3D endoscopy offers no definitive advantage over 2D endoscopy in this simulated model of EDS., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Since its initial description in 1957 as an idiopathic disease, moyamoya disease has proved challenging to treat. Although the basic pathophysiology of this disease involves narrowing of the terminal carotid artery with compensatory angiogenesis, the molecular and cellular mechanisms underlying these changes are far more complex. In this article, the authors review the literature on the molecular and cellular pathophysiology of moyamoya disease with an emphasis on potential therapeutic targets.

Objective: Traditionally, auditory brainstem implants (ABIs) have been placed via the translabyrinthine or retrosigmoid approaches. In select patients, a modified extended middle cranial fossa (xMCF) approach with tentorial ligation may be advantageous for vestibular schwannoma (VS) resection and auditory rehabilitation. This manuscript describes the application of this modification of the MCF approach for simultaneous VS resection and ABI placement., Patients: Patients with neurofibromatosis type 2, profound bilateral sensorineural hearing loss, single functioning sigmoid/jugular venous system, and giant (>4 cm) VS., Interventions: Simultaneous VS resection and ABI placement via a modified xMCF approach with tentorial ligation., Main Outcome Measures: Extent of tumor removal and brainstem decompression, access to lateral recess of the fourth ventricle, functional hearing improvement, surgical complications., Results: Two patients met indications and underwent surgery. There were no immediate or delayed surgical complications. Both had subtotal tumor removal with significant decompression of the brainstem and ABI placement. One patient achieved voice and environmental sound awareness at 35 to 55 dbHL across frequencies. The second patient presented with failure to thrive and multiple lower cranial neuropathies in addition to the above-listed indications. She was hospitalized multiple times after surgery due to failure to thrive and recurrent aspiration pneumonia. Her device was never activated, and she expired 1 year after surgery., Conclusions: The xMCF with tentorial ligation is an additional approach for tumor resection and ABI placement in selected patients with neurofibromatosis type 2. Future studies will further define when this approach is most applicable as well as the challenges and pitfalls., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Brain retraction is a necessary yet potentially damaging requirement of accessing lesions located in deep structures. The development of minimally-invasive tubular retractors (MITRs) provides the theoretical advantage of maximizing visualization of and access to deep-seated lesions, all while minimizing collateral tissue damage. These advantages make MITRs preferable to traditional bladed retractors in the majority of deep-seated lesions. Several commercially-available MITR systems currently exist and have been shown to aid in achieving excellent outcomes with acceptable safety profiles. Nevertheless, important drawbacks to currently-available MITR systems exist. Continued pursuit of an ideal MITR system that provides maximal visualization and access to deep-seated lesions while minimizing retraction-related tissue damage is therefore important. In this review, we discuss the historical development of MITRs, the advantages of MITRs compared to traditional bladed retractors, and opportunities to improve the development of prospective MITRs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mr. Anthony Larson has no conflicts of interest to disclose. Dr. Andrew Grande serves as uncompensated consultants for Minnetronix Medical Inc. (St. Paul, MN, USA). Dr. Grande has never received or requested financial compensation from Minnetronix Medical Inc. Dr. Mario Zuccarello is unpaid advisor to and has received research support from Minnetronix Medical Inc. There are no other conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure., Objective: To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials., Methods: Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n = 84) were compared to STICH II all lobar cases (n = 259) for volumetric analyses. All MISTIE III surgical patients (n = 240) were compared to both STICH I and II (n = 722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment., Results: End-of-treatment ICH volume ≤28.8 mL in MISTIE III and ≤30.0 mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180 d (P = .01 and P = .003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180 d with STICH I and II (P = .0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure., Conclusion: Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window., (© Congress of Neurological Surgeons 2021.)

Background and Purpose: Cervical spine axial MRI T2-hyperintense fluid signal of the anterior median fissure and round hyperintense foci resembling either the central canal or base of the anterior median fissure are associated with a craniocaudad sagittal line, also simulating the central canal. On the basis of empiric observation, we hypothesized that hyperintense foci, the anterior median fissure, and the sagittal line are seen more frequently in patients with Chiari malformation type I, and the sagittal line may be the base of the anterior median fissure in some patients., Materials and Methods: Saggital line incidence and the incidence/frequency of hyperintense foci and anterior median fissure in 25 patients with Chiari I malformation and 25 contemporaneous age-matched controls were recorded in this prospective exploratory study as either combined (hyperintense foci+anterior median fissure in the same patient), connected (anterior median fissure extending to and appearing to be connected with hyperintense foci), or alone as hyperintense foci or an anterior median fissure. Hyperintense foci and anterior median fissure/patient, hyperintense foci/anterior median fissure ratios, and anterior median fissure extending to and appearing to be connected with hyperintense foci were compared in all, in hyperintense foci+anterior median fissure in the same patient, and in anterior median fissure extending to and appearing to be connected with hyperintense foci in patients with Chiari I malformation and controls., Results: Increased sagittal line incidence (56%), hyperintense foci (8.5/patient), and anterior median fissure (4.0/patient) frequency were identified in patients with Chiari I malformation versus controls (28%, 3.9/patient, and 2.7/patient, respectively). Increased anterior median fissure/patient, decreasing hyperintense foci/anterior median fissure ratio, and increasing anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified in Chiari subgroups. A 21%-58% increase in observed anterior median fissure extending to and appearing connected to hyperintense foci in the entire cohort and multiple sagittal line subgroups compared with predicted occurred., Conclusions: In addition to the anticipated increased incidence/frequency of sagittal line and hyperintense foci in patients with Chiari I malformation, an increased incidence and frequency of anterior median fissure and anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified. We believe an anterior median fissure may contribute to a saggital line appearance in some patients with Chiari I malformation. While thin saggital line channels are usually ascribed to the central canal, we believe some may be due to the base of the anterior median fissure, created by pulsatile CSF hydrodynamics., (© 2021 by American Journal of Neuroradiology.)

Intracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury. Here, we longitudinally profiled blood and cerebral hematoma effluent from a patient enrolled in the Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation trial, offering a rare window into the local and systemic immune responses to acute brain injury. Using single-cell RNA-Seq (scRNA-Seq), this is the first report to our knowledge that characterized the local cellular response during ICH in the brain of a living patient at single-cell resolution. Our analysis revealed shifts in the activation states of myeloid and T cells in the brain over time, suggesting that leukocyte responses are dynamically reshaped by the hematoma microenvironment. Interestingly, the patient had an asymptomatic rebleed that our transcriptional data indicated occurred prior to detection by CT scan. This case highlights the rapid immune dynamics in the brain after ICH and suggests that sensitive methods such as scRNA-Seq would enable greater understanding of complex intracerebral events.

The enantioselective functionalization of nonactivated enantiotopic secondary C-H bonds is one of the greatest challenges in transition-metal-catalyzed C-H activation proceeding by an inner-sphere mechanism. Such reactions have remained elusive within the realm of Pd 0 catalysis. Reported here is the unique reactivity profile of the IBiox ligand family in the Pd 0 -catalyzed intramolecular arylation of such nonactivated secondary C-H bonds. Chiral C 2 -symmetric IBiox ligands led to high enantioselectivities for a broad range of valuable indane products containing a tertiary stereocenter, as well as the arylation of secondary C-H bonds adjacent to amides. Depending on the amide substituents and upon control of reaction time, indanes containing labile tertiary stereocenters were also obtained with high enantioselectivities. Analysis of the steric maps of the IBiox ligands indicated that the level of enantioselectivity correlates with the difference between the two most occupied and the two less occupied space quadrants, and provided a blueprint for the design of even more efficient ligands., (© 2020 Wiley-VCH GmbH.)

Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14 + monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort. Initially, hematoma myeloid cells expressed a robust anabolic proinflammatory profile characterized by activation of hypoxia-inducible factors (HIFs) and expression of genes encoding immune factors and glycolysis. Subsequently, inflammatory gene expression decreased over time, whereas anti-inflammatory circuits were maintained and phagocytic and antioxidative pathways up-regulated. During this transition to immune resolution, glycolysis gene expression and levels of the potent proresolution lipid mediator prostaglandin E 2 remained elevated in the hematoma, and unexpectedly, these elevations correlated with positive patient outcomes. Ex vivo activation of human macrophages by ICH-associated stimuli highlighted an important role for HIFs in production of both inflammatory and anti-inflammatory factors, including PGE 2 , which, in turn, augmented VEGF production. Our findings define the time course of myeloid activation in the human brain after ICH, revealing a conserved progression of immune responses from proinflammatory to proresolution states in humans after brain injury and identifying transcriptional programs associated with neurological recovery., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Spontaneous supratentorial intracranial hemorrhage is extremely disabling and is associated with high mortality. Primary treatment for patients with this disease process is maximal medical management with blood pressure control and correction of clotting disorders due to comorbid conditions or medications. Over the past decade, significant strides have been made in understanding the benefits of surgical intervention in the treatment of intracranial hemorrhage through multiple clinical trials. In this article, we review the evolution of surgical treatments beginning with the STICH trials, discuss new developments with minimally invasive surgical strategies, and provide a brief update regarding ongoing trials and future directions in the treatment of spontaneous supratentorial intracranial hemorrhage., Competing Interests: None., (Thieme. All rights reserved.)

Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression. Mutations of the NF2 gene are strongly associated with NF2 diagnosis, leading to benign proliferative conditions such as vestibular schwannomas and meningiomas. Unfortunately, even though these tumors are benign, they are associated with significant morbidity and the potential for early mortality. In this review, we aim to encompass meningiomas and vestibular schwannomas as they pertain to NF2 by assessing molecular genetics, common tumor types, and tumor pathogenesis.

Objective: Compare outcomes of middle cranial fossa approach (MCF) to vestibular schwannoma (VS) resection in patients 60 years of age and older to patients under 60., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Charts of 216 consecutive VS patients over 18 years of age were reviewed to identify 67 patients who underwent MCF approach to VS resection between 2006 and 2017., Intervention(s): Age at time of surgery., Main Outcome Measure(s): Measured outcomes included postoperative hearing results, facial nerve function, length of hospital stay, wound complications, cerebrospinal fluid leak, myocardial infarction, cerebrovascular accident, seizure, deep vein thrombosis, 30-day readmission, and return to operating room., Results: Sixty-seven patients underwent VS resection via MCF approach including 16 patients > = 60 years (mean 64.4 SD 3.3) and 51 patients < 60 years (mean 45.7 SD 10.2). Between these two groups, there were no differences in sex, tumor laterality, tumor size (10.4 mm versus 9.8 mm, p = 0.6), or other demographic characteristics. Postoperatively, there were no differences between groups in complication rates. Rates of HB 1 or 2 facial nerve function were similar (93.8% versus 88.2%, p = 0.7) as were rates of maintenance of class A or B hearing (58.3% versus 44.4%, p = 0.7)., Conclusions: Patients over 60 undergoing MCF for VS resection experienced similar rates of postoperative complications, facial nerve outcomes, and hearing preservation compared with younger patients. MCF for VS may be considered in the older population. Further research is warranted to evaluate appropriate limitations for this approach based on age.

Background: Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure was recently tested in a large phase III randomized trial showing a significant probability of functional benefit in those cases that reached the goal hematoma evacuation of ≤15 mL residual (or ≥70% removal). Benefit of thrombolysis was also identified in cases with large intraventricular hemorrhage, and achieving at least 85% volume reduction in the Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial., Objective: To protocolize steps in the MISTIE and CLEAR procedures in order to maximize hematoma evacuation and minimize complications., Methods: We articulate data-driven lessons and expert opinions surrounding the factors of patient selection, catheter placement, and dosing, which impacted safety and surgical performance in the MISTIE and CLEAR trials., Results: Modifiable factors to maximize evacuation efficiency include optimizing catheter placement and pursuing aggressive dosing to achieve treatment goals, while strictly adhering to the safety steps as articulated in the respective trials. Prognostic factors that are viewed as nonmodifiable include greater initial intracerebral hemorrhage volume with irregular shape, smaller intraventricular bleeds, and the uncommon but consequential development of new bleeding during the dosing period despite strict protocol adherence., Conclusions: Surgeon education in this tutorial is aimed at maximizing the benefit of the MISTIE and CLEAR procedures by reviewing case selection, safety steps, treatment objectives, and technical nuances. Key lessons include stability imaging, etiology screening, and technical adherence to the protocol in order to achieve defined thresholds of evacuation., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background/objective: Intracerebral hemorrhage (ICH) patients commonly have concomitant white matter lesions (WML) which may be associated with poor outcome. We studied if WML affects hematoma expansion (HE) and post-stroke functional outcome in a post hoc analysis of patients from randomized controlled trials., Methods: In ICH patients from the clinical trials MISTIE II and CLEAR III, WML grade on diagnostic computed tomography (dCT) scan (dCT, < 24 h after ictus) was assessed using the van Swieten scale (vSS, range 0-4). The primary outcome for HE was > 33% or > 6 mL ICH volume increase from dCT to the last pre-randomization CT (< 72 h of dCT). Secondary HE outcomes were: absolute ICH expansion, > 10.4 mL total clot volume increase, and a subgroup analysis including patients with dCT < 6 h after ictus using the primary HE definition of > 33% or > 6 mL ICH volume increase. Poor functional outcome was assessed at 180 days and defined as modified Rankin Scale (mRS) ≥ 4, with ordinal mRS as a secondary endpoint., Results: Of 635 patients, 55% had WML grade 1-4 at dCT (median 2.2 h from ictus) and 13% had subsequent HE. WML at dCT did not increase the odds for primary or secondary HE endpoints (P ≥ 0.05) after adjustment for ICH volume, intraventricular hemorrhage volume, warfarin/INR > 1.5, ictus to dCT time in hours, age, diabetes mellitus, and thalamic ICH location. WML increased the odds for having poor functional outcome (mRS ≥ 4) in univariate analyses (vSS 4; OR 4.16; 95% CI 2.54-6.83; P < 0.001) which persisted in multivariable analyses after adjustment for HE and other outcome risk factors., Conclusions: Concomitant WML does not increase the odds for HE in patients with ICH but increases the odds for poor functional outcome., Clinical Trial Registration: http://www.clinicaltrials.gov trial-identifiers: NCT00224770 and NCT00784134.

Objective: Compare outcomes for patients who were seen via telemedicine visits after otology/neurotology surgical procedures with those who were seen in traditional office visits., Study Design: Retrospective case review., Setting: Tertiary care academic medical center., Patients: Inclusion criteria were patients who underwent otologic/neurotologic surgery and were seen in at least one telemedicine visit for postoperative care., Intervention (s): Telemedicine visit for postoperative care., Main Outcome Measure (s): Comparison of the number of patient calls, unplanned visits, and delayed complications between telemedicine patients and controls matched for age, procedure, and American Society of Anesthesiologists (ASA) status., Results: Eighteen patients were seen in telemedicine visits postoperatively after the following otologic/neurotologic surgical procedures: cochlear implant surgery (10), vestibular schwannoma resection (4), combined middle fossa and transmastoid cerebrospinal fluid (CSF) leak repair (2), middle fossa repair of superior canal dehiscence (1), and stapedectomy (1). All telehealth visits were for the second postoperative visit. The mean number of patient calls after surgery was 2.3 for the telemedicine group and 1.9 for matched controls which was not a statistically significant difference (p = 0.466). Both groups each had two patients who went to the emergency room, with one in each group being admitted. There was one delayed complication in the control group., Conclusion: Our preliminary experience suggests telemedicine may be used safely in caring for patients after otologic/neurotologic surgery, though it may be associated with more patient phone calls. Further study and experience, including assessing patient satisfaction, will clarify the future role of telemedicine in otology and neurotology.

Background: Petroclival tumors and ventrolateral lesions of the pons present unique surgical challenges. This cadaveric study provides qualitative and quantitative anatomic comparison for an anterior petrous apicectomy through the transcranial middle fossa (TMF) and expanded endoscopic transsphenoidal-transclival approaches., Methods: In 10 silicone-injected heads, the petrous apex and clivus were drilled extradurally using middle fossa and endonasal approaches. With in situ and frameless stereotactic navigation, we defined consistent points to compare working areas, bone removal volumes, approach angles, and surgical freedom., Results: Mean exposed TMF area (21.03 ± 3.46 cm 2 ) achieved a 44.71 ± 4.13° working angle to the brainstem between cranial nerves V and VI. Kawase's rhomboid area measured 1.76 ± 0.34 cm 2 , and bone removal averaged 1.20 ± 0.12 cm 3 at the petrous apex. Surgical freedom on the lateral brainstem was higher halfway between cranial nerves V and VI at the center of the rhomboid compared with midline at the basilar sulcus (P < 0.01). After clivectomy and petrous apicectomy, mean exposed expanded endoscopic transsphenoidal-transclival area was 5.29 ± 0.66 cm 2 . Approach from either nostril showed no statistically significant differences in surgical freedom at the foramen lacerum and midpoint basilar sulcus. At the petrous apex, bone volume removed and area exposed were significantly larger for the TMF approach (P < 0.001)., Conclusions: Expanded transclival anterior petrosectomy through the TMF approach provides an adequate corridor to lesions in the upper ventrolateral pons. The expanded endoscopic transsphenoidal-transclival approach better fits midline lesions not extending laterally beyond cranial nerve VI and C3 carotid when evaluating normal anatomic parameters., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To examine the association between operative duration and complications after vestibular schwannoma (VS) surgery., Study Design: Retrospective chart review., Setting: Tertiary referral center., Patients: One hundred forty-eight patients undergoing vestibular schwannoma resection in a single institution., Intervention: Vestibular schwannoma resection., Main Outcome Measures: Operative duration, surgical approach, tumor size, and postoperative complications., Results: Forty-one patients underwent middle cranial fossa (MCF) approach, 46 underwent translabyrinthine (TL) approach, and 61 underwent retrosigmoid (RS) approach. The mean operative duration overall was 407 minutes (MCF-339 min, TL-450 min, RS 420 min). When controlling for tumor size, there was no difference in procedure duration by approach (OR 0.92, CI 0.82-1.02, p=0.11).When controlling for approach, there was a significant increase in procedure duration by tumor size (OR 1.36, CI 1.23-1.50, p < 0.0001). Increased procedure duration was not associated with 30-day readmission (p = 0.82), cerebrospinal fluid leak (CSF) (p = 0.84), return to the operating room (p = 0.75), postoperative deep vein thrombosis (p = 1.0), postoperative stroke (p = 0.23), or postoperative wound complications (p = 0.70). Longer operative time was associated with increased hospital length of stay (p = 0.04). However, when controlling for tumor size and surgical approach, hospital length of stay was no longer associated with increased procedure duration (OR 1.15, CI 0.98-1.33, p = 0.3)., Conclusion: Increased operative duration was associated with larger tumor size; however contrary to previous reports, increased operative duration was not associated with postoperative complications.

Objective: Determine whether elevated body mass index (BMI) is associated with postoperative complications after vestibular schwannoma (VS) surgery., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Two hundred six patients undergoing surgery for VS between 2010 and 2017, grouped into obese and nonobese patients., Intervention: Surgery for VS resection., Main Outcome Measures: Postoperative facial nerve outcomes, length of hospital stay, presence of postoperative cerebrospinal fluid leak, 30-day readmission, return to the operating room, wound complications, cardiovascular and thromboembolic complications., Results: After excluding 1 patient for missing BMI, our cohort included 205 patients. Seventy-nine patients (38.5%) were obese (mean BMI 36.2 kg/m, range 30-55.1) and the remaining 126 (61.5%) were nonobese (mean BMI 25.0, range 18.8-29.8 kg/m). Compared with nonobese patients, obesity was not associated with postoperative cerebrospinal fluid leak (OR 1.1, 95% CI 0.93-1.1), length of hospital stay (OR 0.98, 95% CI 0.65-1.47), 30-day readmission rates (1.04, 95% CI 0.95-1.14), return to operating room (OR 1.05, 95% CI 0.98-1.11), or other wound-related complications (OR 0.99, 95% CI 0.94-1.04)., Conclusion: In this cohort, elevated BMI was not associated with an increased risk for postoperative complications after VS surgery. Our findings may mitigate concerns associated with surgical management of VS in obese patients.

Objective  Evaluate the cerebrospinal fluid (CSF) leak rate after the middle cranial fossa (MCF) approach to vestibular schwannoma (VS) resection. Design  Retrospective case series. Setting  Quaternary referral academic center. Participants  Of 161 patients undergoing the MCF approach for a variety of skull base pathologies, 66 patients underwent this approach for VS resection between 2007 and 2017. Main Outcome Measure  Postoperative CSF leak rate. Results  There were two instances of postoperative CSF leak (3.0%). Age, gender, and BMI were not significantly associated with CSF leak. In the two cases with CSF leakage, tumors were isolated to the internal auditory canal (IAC) and both underwent gross total resection. Both CSF leaks were successfully treated with lumbar drain diversion. For the 64 cases that did not have a CSF leak, 51 were isolated to the IAC, 1 was located only in the cerebellopontine angle (CPA), and 12 were located in both the IAC and CPA. 62 patients underwent gross total resection and 2 underwent near-total resection. Mean maximal tumor diameter in the CSF leak group was 4.5 mm (range: 3-6 mm) versus 10.2 mm (range: 3-19 mm) in patients with no CSF leak ( p  = 0.03). Conclusions  The MCF approach for VS resection is a valuable technique that allows for hearing preservation and total tumor resection and can be performed with a low CSF leakage rate. This rate of CSF leak is less than the reported rates in the literature in regard to both translabyrinthine and retrosigmoid approaches.

Rationale and Hypothesis: Surgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials., Methods and Design: MISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study., Study Outcomes: The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.