Evaluation of clinical predictors of postoperative outcomes in tegmen defect patients with and without concurrent superior semicircular canal dehiscence and cerebrospinal fluid leak.

OBJECTIVES: Tegmen and superior semicircular canal defects have been well studied, yet the factors contributing to their onset and progression are widely debated. The clinical utility of intraoperative intracranial pressure measurements has yet to be tested. This report aims to use intraoperative opening pressure and concurrent superior semicircular canal dehiscence (SSCD) to analyze factors influencing disease course and clinical outcomes in patients with tegmen dehiscence. METHODS: A retrospective analysis of 61 patients who underwent tegmen defect repair was performed. Multiple variables of interest including body mass index (BMI), presence of SSCD, presence of dural venous sinus stenosis, opening pressure, and acetazolamide therapy use were recorded. The cohort was divided into those with or without concurrent SSCD and those presenting with or without cerebrospinal fluid (CSF) leak for analysis. RESULTS: A linear relationship between opening pressure and BMI (p = 0.009) was noted; however, intraoperative opening pressure was not associated with disease outcome. Concurrent SSCD was present in 25 % of patients, while 62 % presented with CSF leak. The concurrent SSCD group exhibited higher opening pressure, higher likelihood of having dural sinus stenosis, and higher likelihood of being discharged on acetazolamide. The CSF leak group had higher likelihood of obstructive sleep apnea and persistent symptoms. CONCLUSIONS: In patients undergoing tegmen defect repair, concurrent SSCD suggests increased disease severity. The presence of preoperative CSF leak predicts persistent symptoms following repair. BMI is linearly correlated with intracranial pressure in these patients.

The utility of inflammatory biomarkers in predicting overall survival and recurrence in skull base chordoma.

OBJECTIVE: Numerous studies have investigated the impact of inflammatory factors in cancer, yet few attempts have been made to investigate these markers in skull base chordoma (SBC). Inflammatory values including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) can serve as prognostic markers in various cancers. This study aimed to determine whether these inflammatory factors influence overall survival (OS) or progression-free survival (PFS) in patients with primary SBC. METHODS: The electronic medical records of patients with primary SBC who underwent resection from 2001 to 2020 were retrospectively reviewed for the associations of sex, age at diagnosis, preoperative steroid use, tumor volume, extent of resection, adjuvant radiation after surgery, tumor metastasis, Ki-67 index, percent homozygous deletion of 9p23 and percent 1p36 loss, and potential prognostic inflammatory markers of NLR, PLR, LMR, SII, and SIRI with the primary outcome measures of OS and PFS. Maximum log-rank statistical tests were used to determine inflammatory marker thresholds for grouping prior to Kaplan-Meier and Cox proportional hazards analysis for OS and PFS of the elucidated groups. RESULTS: The cohort included 115 primary SBC patients. The mean ± SD tumor volume was 23.0 ± 28.0 cm3, 73% of patients received gross-total resection, 40% received postoperative radiation, 25% had local recurrence, and 6% had subsequent metastatic disease (mean follow-up 47.2 months). Univariable Cox analysis revealed that NLR (p < 0.01), PLR (p = 0.04), LMR (p = 0.04), SII (p < 0.01), and SIRI (p < 0.01) were independently associated with PFS. Additionally, NLR (p = 0.05) and SII (p = 0.03) were significant in multivariable Cox analysis of PFS. However, both univariable and multivariable Cox analysis revealed no correlations with OS. CONCLUSIONS: The routine assessment of inflammatory biomarkers such as NLR and SIRI could have prognostic value in postresection SBC patients.

A comprehensive evaluation of career trajectories of the American Association of Neurological Surgeons William P. Van Wagenen fellows.

Objective: To elucidate the current academic, demographic, and professional factors influencing the career trajectories of the American Association of Neurological Surgeons (AANS) William P. Van Wagenen (VW) fellows while also identifying trends that may influence future fellow selection. Methods: Fifty-five VW fellows were identified from 1968 to 2022 from the AANS website, along with corresponding institutions, countries, and continents of study. Additional variables such as age at selection, accruing additional degrees, neurosurgical subspecialty, the number of publications at the time of selection, funding, and h-index were collected from various publicly available sources. Results: Eighty-five percent of VW fellows were male and had a mean age of 34 ± 2.4 years. Ninety-one percent of fellows chose to study in Europe, and 40% had earned additional degrees. Univariate linear regression demonstrated a positive relationship between the year of selection and both age at selection (p = 0.0094) and the number of publications at hire (p < 0.001), while logistic regression revealed that more recently selected fellows were less likely to study in Europe (p = 0.037) and be of the white race (p = 0.0047). Logistic regression also exhibited a positive trend between the year of selection and both the likelihood that the VW fellow was currently enrolled in another fellowship (p = 0.019) and possessed additional degrees (p = 0.0019). Females were shown to have fewer publications at hire compared to males (p = 0.04). Conclusions: Most Van Wagenen fellows are academically productive members of the neurosurgical community. Increased attention is likely to be placed on both academic, research, and individualized factors when selecting future fellows.

Cross-sectional examination of current and future trends and attributes of the presidents of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons societies.

Objective: The present study aimed to analyze the academic attributes of the presidents of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) over the past four decades to elucidate the trajectories of these societies' leaderships. Methods: Forty-three AANS and 43 CNS presidents of the past four decades were identified. Demographic and research productivity data were collected from publicly available sources. Results: Compared to AANS presidents, CNS presidents were younger (median = 48 years vs. 59.5 years; p < 0.001), had fewer years of practice prior to their election (15 years vs. 28 years; p < 0.001), had higher NIH funding rate (37.2% vs. 11.6%; p = 0.01), and higher rate of practicing at academic institutions (93% vs. 74.4%; p = 0.04). The CNS presidents had a comparable median number of publications at election (AANS: 72 vs. CNS: 94 publications, p = 0.78) but a higher median h-index scores (AANS: 28 vs. CNS: 59; p = 0.04). In the multiple linear regression analysis, vascular subspecialty (ß = 0.21 [95% CI: 0.09-0.34]; p = 0.002) and practicing in a non-academic institution (ß = 0.23 [95% CI: 0.08-0.39]; p = 0.007) were predictors for later election for AANS presidency. Conclusions: We characterized the attributes of AANS and CNS presidents to serve as useful references for career trajectories for junior neurosurgeons and trainees. Research and academic presence seem to be associated with early election to both societies.

Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming.

Cancers commonly reprogram translation and metabolism, but little is known about how these two features coordinate in cancer stem cells. Here we show that glioblastoma stem cells (GSCs) display elevated protein translation. To dissect underlying mechanisms, we performed a CRISPR screen and identified YRDC as the top essential transfer RNA (tRNA) modification enzyme in GSCs. YRDC catalyzes the formation of N6-threonylcarbamoyladenosine (t6A) on ANN-decoding tRNA species (A denotes adenosine, and N denotes any nucleotide). Targeting YRDC reduced t6A formation, suppressed global translation and inhibited tumor growth both in vitro and in vivo. Threonine is an essential substrate of YRDC. Threonine accumulated in GSCs, which facilitated t6A formation through YRDC and shifted the proteome to support mitosis-related genes with ANN codon bias. Dietary threonine restriction (TR) reduced tumor t6A formation, slowed xenograft growth and augmented anti-tumor efficacy of chemotherapy and anti-mitotic therapy, providing a molecular basis for a dietary intervention in cancer treatment.

Assessment of the safety and efficacy of the Zoom 45 and 55 reperfusion catheters for medium and distal mechanical thrombectomies: A multi-institutional study.

INTRODUCTION: The Zoom aspiration catheters harbor novel dimensions and construction to enhance trackability and deliverability. In addition, a beveled tip may improve thrombus interaction and aspiration force for a set inner diameter. This study evaluates their utility in medium and distal vessel occlusions. OBJECTIVE: To evaluate the safety and efficacy of Zoom 45 and 55 aspiration catheters in medium and distal vessel thrombectomy. METHODS: Patients treated for distal vessel occlusions via mechanical thrombectomy utilizing either the Zoom 45/55 catheter or a historical control catheter between 2021-2022 at two institutions were included in this study. Medium and distal occlusions were defined as any anterior or posterior cerebral artery branch as well as the M2-4 segment of the middle cerebral artery (MCA). Preprocedural, procedural, and postprocedural variables were obtained. RESULTS: Thirty-eight patients underwent thrombectomy with Zoom 45 or 55 catheters; four had multiple occluded vessels. Occlusion location included the M2 in 32 cases, M3-4 in 7 cases, A2 in 2 cases and P2 in 1 case. The mean number of passes per occlusion was 1.6 and overall successful reperfusion (TICI 2b or greater) was achieved in 84 % of cases. There were no symptomatic procedure-related complications such as perforation or post-procedural symptomatic ICH. Modified Rankin scores rates of 0-2, 3-5, and 6 at three months post-procedure were 35.7 %, 21.4 %, and 42.9 %, respectively. CONCLUSIONS: The Zoom beveled tip aspiration catheters are safe and effective for more challenging medium and distal vessel occlusions.

Surgical intervention ≤ 24 hours versus > 24 hours after injury for the management of acute traumatic central cord syndrome: a systematic review and meta-analysis.

OBJECTIVE: The objective was to evaluate the efficacy, outcomes, and complications of surgical intervention performed within 24 hours (≤ 24 hours) versus after 24 hours (> 24 hours) in managing acute traumatic central cord syndrome (ATCCS). METHODS: Articles pertinent to the study were retrieved from PubMed, Scopus, Web of Science, and Cochrane. The authors performed a systematic review and meta-analysis of treatment procedures and outcomes according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMSA) guidelines. RESULTS: Seven articles comprising 488 patients were included, with 188 (38.5%) patients in the ≤ 24-hour group and 300 (61.5%) in the > 24-hour group. Significant differences were not found between groups in terms of demographic characteristics, injury mechanism, spinal cord compression level, neuroimaging features, and the American Spinal Injury Association (ASIA) motor score at admission. Both groups had a similar approach to surgery and steroid administration. The surgical complication rate was significantly higher in the > 24-hour group (4.5%) compared to the ≤ 24-hour group (1.2%) (p = 0.05). Clinical follow-up duration was similar at 12 months (interquartile range 3-36) for both groups (p > 0.99). The ≤ 24-hour group demonstrated a not statistically significant greater improvement in ASIA motor score, with a mean difference of 12 (95% CI -20.7 to 44.6) compared to the > 24-hour group. CONCLUSIONS: The present study indicates potential advantages of early (≤ 24 hours) surgery in ATCCS patients, specifically in terms of lower complication rates. However, further research is needed to confirm these findings and their clinical implications.

Exoscope-based supracerebellar infratentorial approach for a pineal meningioma in the prone position.

The supracerebellar infratentorial (SCIT) approach is a well-described corridor to lesions in the quadrigeminal cistern, pineal gland, and dorsal midbrain. It can be performed in the prone or sitting position. The sitting position offers the benefit of gravity retraction of the cerebellum but comes at the expense of nonergonomic hand positioning and the potential risk of air embolism. The 3D exoscope is an alternative to the operating microscope and permits the SCIT approach in the prone position with excellent visualization. This video demonstrates exoscope-based SCIT approach for resection of a pineal meningioma in the prone position. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23155.

Toward Optimized and Cost-Efficient Protocols for Inferior Petrosal Sinus Sampling in the Diagnosis of Cushing Disease.

BACKGROUND AND OBJECTIVE: Conventional protocols for inferior petrosal sinus sampling (IPSS) during the workup of hypercortisolemia require adrenocorticotrophic hormone (ACTH) measurement at multiple time points with corticotropic-releasing hormone (CRH) used as a stimulator. Modernized evidence-based protocols must also reflect the increased utilization of desmopressin (DDAVP) for ACTH stimulation as the manufacturing shortage of traditionally used CRH continues. We model the diagnostic accuracy and potential economic savings of DDAVP utilization and reduced time point sampling. METHODS: A single-institution, retrospective review of patients undergoing IPSS between 2007 and 2021 was performed. A computational search for the minimal set of time points which preserves conventional diagnostic accuracy was performed by testing all 1 through 5-point combinations generated using a binomial expansion. Economic savings were modeled using a publicly available hospital chargemaster. RESULTS: A total of 50 patients qualified for inclusion, 47 of whom were diagnosed with Cushing disease and 3 with ectopic Cushing syndrome. Single-point diagnostic accuracy for DDAVP-stimulated tests was 71.4%-92.9%, and seven 2-point combinations (5-25 procedural minutes) were found, which preserved conventional diagnostic accuracy. Single-point accuracy for CRH-stimulated tests was 67.9%-89.3%, and two 2-point combinations ( t = -15, t = +2 and t = -15, t = +10) preserved accuracy. For every time point removed, the cost of ACTH laboratory tests was reduced by $507 from $3042 for 6-point IPSS). The shortest and most economical stimulator and time point combination that preserved conventional accuracy was DDAVP sampling at t = 0 and t = +5 or t = +2 and t = +5 minutes, which cost $2028 total compared with the most expensive 6-point IPSS option with CRH ($6392). CONCLUSION: DDAVP is a cost-efficient and effective alternative to CRH during IPSS. Our results encourage prospective evaluation of potentially fewer sampling time points in the interest of time and cost efficiency balanced with preserved accuracy.

An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma.

Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced by the hallmark histone mutation H3K27M, which results in aberrantly permissive activation of oncogenic signaling pathways. Previous studies of diffuse midline glioma with altered H3K27 (DMG-H3K27a) have shown that the RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), is critical for tumor growth. Further downstream effectors of ERK5 and their role in DMG-H3K27a metabolic reprogramming have not been explored. We establish that ERK5 is a critical regulator of cell proliferation and glycolysis in DMG-H3K27a. We demonstrate that ERK5 mediates glycolysis through activation of transcription factor MEF2A, which subsequently modulates expression of glycolytic enzyme PFKFB3. We show that in vitro and mouse models of DMG-H3K27a are sensitive to the loss of PFKFB3. Multi-targeted drug therapy against the ERK5-PFKFB3 axis, such as with small-molecule inhibitors, may represent a promising therapeutic approach in patients with pediatric diffuse midline glioma.

Idiopathic De Novo Arteriovenous Malformation: A Rare Acquired Intracranial Lesion.

The de novo development of cerebral arteriovenous malformations (AVMs) in adults is an exceedingly rare event that has prompted the theory that a "second hit" is required to induce AVM formation. The authors document development of an occipital AVM in an adult a decade and a half after a brain magnetic resonance imaging (MRI) disclosed no abnormality. A 31-year-old male with a family history of AVMs and a 14-year history of migraines with visual auras and seizures presented to our service. Because of the onset of a first seizure and migraine headaches at age 17, the patient underwent high-resolution MRI that showed no intracranial lesion. After 14 years of progressively worsening symptoms, he underwent a repeat MRI that demonstrated a new de novo Spetzler-Martin grade 3 left occipital AVM. The patient received anticonvulsants and underwent Gamma Knife radiosurgery for his AVM. This case suggests that patients with seizures or persistent migraine headaches should have periodic repeat neuroimaging to exclude the development of a vascular cause despite an initial negative MRI.

Outcomes and Treatment Algorithm in Glioblastoma Patients 80 Years and Older.

OBJECTIVE: The current standard of care for patients with glioblastoma (GBM) is maximal safe resection followed by adjuvant radiation therapy with concurrent temozolomide chemotherapy. Previous studies that identified this treatment regimen focused on younger patients with GBM. The proportion of patients with GBM over the age of 80 years is increasing. We investigate whether elderly patients benefit from the current standard of care with additional maximal safe resection. METHODS: Clinical, operative, radiographic, demographic, genetic, and outcomes data were retrospectively collected for patients treated for histologically confirmed World Health Organization grade 4 GBM at University of Pittsburgh Medical Center from 2009 to 2020. Only patients 80 years and older were included (n = 123). Statistically significant values were set at P < 0.05. RESULTS: A univariate Cox proportional hazards analysis of GBM patients aged >80 years identified the use of temozolomide, radiation, Karnofsky Performance Status (KPS) > 70, and methylguanine DNA methyltransferase methylation with increased overall survival (OS). Further multivariate Cox proportional hazards model analysis showed that the variables identified in the univariate analysis passed multicollinearity testing, and that use of temozolomide, KPS >70, and gross total resection were shown to significantly impact survival. Survival analysis showed that patients with biopsy alone had a shorter median OS compared with patients who received resection, temozolomide, and radiation (P < 0.0001, median OS 1.6 vs. 7.5 months). Additionally, patients who underwent biopsy and then received temozolomide and radiation had a shorter median OS when compared with patients who received resection, temozolomide, and radiation (P = 0.0047, median OS 3.6 vs. 7.5 months). CONCLUSIONS: For elderly patients with KPS >70, GTR followed by radiation and temozolomide is associated with maximum OS.

Application of Radiomics to the Differential Diagnosis of Temporal Bone Skull Base Lesions: A Pilot Study.

BACKGROUND: Temporal bone skull base pathologies represent a complex differential because they can be radiographically obscure and difficult to diagnose without biopsy. Radiomics involves the use of mathematical quantification of imaging data beyond simple intensity, size, and location to inform diagnosis and prognosis. We examined the feasibility of using radiomic parameters to help predict temporal bone tumor type. METHODS: A total of 117 radiomic parameters were analyzed from 5 magnetic resonance imaging sequences (T1 without contrast, T1 with contrast, T2, fluid-attenuated inversion recovery, apparent diffusion coefficient [ADC]) for each tumor. Statistical analysis was used to delineate known primary, metastatic/secondary, and lymphoma lesions using radiomics. RESULTS: The mean tumor volumes for the 14 primary, 12 secondary, and 8 lymphoma lesions were 2.98 ± 2.11, 3.28 ± 2.31, and 12.16 ± 7.1 cm3, respectively (P = 0.2). No significant differences in mean intensity values for any sequence helped distinguish tumors (P > 0.05), but 6 radiomic parameters were significantly correlated with diagnostic accuracy. Discriminant analysis using a stepwise algorithm generated a model where radiomic parameters for T1 cluster prominence, ADC dependence nonuniformity, T1 with contrast zone percentage, and ADC informational measure of correlation 2 achieved the best predictive model (P = 0.0001). These significant characteristics were often indirect measures of tumor heterogeneity on different magnetic resonance imaging sequences. CONCLUSIONS: These data suggest that quantitative measures of tumor heterogeneity can be discriminatory of pathology and might be integrated into clinical workflow. Although this pilot study requires further validation, these data support the exploration of radiomics in temporal bone radiographic diagnostics.

United States Neurosurgery Department Program Directors: A Cross-Sectional Evaluation of Current and Future Trends and Attributes.

BACKGROUND: While United States (U.S.) neurosurgery residency programs have been subject to many studies, none have focused solely on the program directors (PDs). We aim to analyze the demographic, educational, and academic attributes of this cohort to understand current and future trends of PDs. METHODS: One hundred sixteen neurosurgeons listed as PDs at U.S. accredited neurosurgical residency training programs as of August 2022 were assessed. Descriptive data including age upon acceptance of role, gender, and h-index were collected from publicly available sources. RESULTS: Most PDs matriculated to their positions before the age of 45 years, were male, and had been hired internally. Approximately 25% of PDs had earned an additional degree. Departments with higher aggregate h-indexes were more likely to hire PDs with higher average publications per year (P < 0.001) and have a higher h-index (P < 0.001). PD subspecialty influenced h-index (P < 0.05) and total average publications per year (P < 0.05) with neuro-oncology subspecialists having higher averages in both. More recently hired PDs had a higher average number of publications per year (P < 0.05) and were more likely to hold an additional degree (odds ratio 1.14, P < 0.05). Female PDs were hired at a younger age (P < 0.05). CONCLUSIONS: Neurosurgery PDs typically rise to their position after 10 years of practice and more recent PD hires are more likely to have additional degrees and more publications. As academic neurosurgery becomes more competitive, increased academic productivity and acquisition of additional degrees will become increasingly necessary.

Age-dependent vestibular cingulate-cerebral network underlying gravitational perception: a cross-sectional multimodal study.

BACKGROUND AND OBJECTIVES: The cingulate gyrus (CG) is a frequently studied yet not wholly understood area of the human cerebrum. Previous studies have implicated CG in different adaptive cognitive-emotional functions and fascinating or debilitating symptoms. We describe an unusual loss of gravity perception/floating sensation in consecutive persons with drug-resistant epilepsy undergoing electrical cortical stimulation (ECS), network analysis, and network robustness mapping. METHODS: Using Intracranial-EEG, Granger causality analysis, cortico-cortical evoked potentials, and fMRI, we explicate the functional networks arising from this phenomenon's anterior, middle, and posterior cingulate cortex. RESULTS: Fifty-four icEEG cases from 2013 to 2019 were screened. In 40.7% of cases, CG was sampled and in 22.2% the sampling was bilateral. ECS mapping was carried out in 18.5% of the entire cohort and 45.4% of the cingulate sampled cases. Five of the ten CG cases experienced symptoms during stimulation. A total of 1942 electrodes were implanted with a median number of 182 electrode contacts per patient (range: 106-274). The electrode contacts sampled all major cortex regions. Sixty-three contacts were within CG. Of those, 26 were electrically stimulated; 53.8% of the stimulated contacts produced positive responses, whereas 46.2% produced no observable responses. Our study reports a unique perceptive phenomenon of a subjective sense of weightlessness/floating sensation triggered by anterior and posterior CG stimulation, in 30% of cases and 21.42% of electrode stimulation sites. Notable findings include functional connections between the insula, the posterior and anterior cingulate cortex, and networks between the middle cingulate and the frontal and temporal lobes and the cerebellum. We also postulate a vestibular-cerebral-cingulate network responsible for the perception of gravity while suggesting that cingulate functional connectivity follows a long-term developmental trajectory as indicated by a robust, positive correlation with age and the extent of Granger connectivity (r = 0.82, p = 0.0035). DISCUSSION: We propose, in conjunction with ECS techniques, that a better understanding of the underlying gravity perception networks can lead to promising neuromodulatory clinical applications. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence for CG's involvement in the higher order processing of gravity perception and related actions.