360° around the orbit: key surgical anatomy of the microsurgical and endoscopic cranio-orbital and orbitocranial approaches.

OBJECTIVE: Several pathologies either invade or arise within the orbit. These include meningiomas, schwannomas, and cavernous hemangiomas among others. Although several studies describing various approaches to the orbit are available, no study describes all cranio-orbital and orbitocranial approaches with clear, surgically oriented anatomical descriptions. As such, this study aimed to provide a comprehensive guide to the microsurgical and endoscopic approaches to and through the orbit. METHODS: Six formalin-fixed, latex-injected cadaveric head specimens were dissected in the surgical anatomy laboratory at the authors' institution. In each specimen, the following approaches were modularly performed: endoscopic transorbital approaches (ETOAs), including a lateral transorbital approach and a superior eyelid crease approach; endoscopic endonasal approaches (EEAs), including those to the medial orbit and optic canal; and transcranial approaches, including a supraorbital approach, a fronto-orbital approach, and a 3-piece orbito-zygomatic approach. Each pertinent step was 3D photograph-documented with macroscopic and endoscopic techniques as previously described. RESULTS: Endoscopic endonasal approaches to the orbit afforded excellent access to the medial orbit and medial optic canal. Regarding ETOAs, the lateral transorbital approach afforded excellent access to the floor of the middle fossa and, once the lateral orbital rim was removed, the cavernous sinus could be dissected and the petrous apex drilled. The superior eyelid approach provides excellent access to the anterior cranial fossa just superior to the orbit, as well as the dura of the lesser wing of the sphenoid. Craniotomy-based approaches provided excellent access to the anterior and middle cranial fossa and the cavernous sinus, except the supraorbital approach had limited access to the middle fossa. CONCLUSIONS: This study outlines the essential surgical steps for major cranio-orbital and orbitocranial approaches. Endoscopic endonasal approaches offer direct medial access, potentially providing bilateral exposure to optic canals. ETOAs serve as both orbital access and as a corridor to surrounding regions. Cranio-orbital approaches follow a lateral-to-medial, superior-to-inferior trajectory, progressively allowing removal of protective bony structures for proportional orbit access.

Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis.

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved. We performed an electronic search on Web of Science to identify the top 100 published and indexed articles with the highest number of citations discussing the pathogenesis of AVMs. This study yielded 1863 articles, of which the top 100 were selected based on the highest total citation count. These articles included 24% basic science, 46% clinical, and 30% review articles. The most-cited article was a clinical article from 2003, and the most recent was published in 2022. The median number of authors was 6, with the highest being 46 for a clinical article. The top 5 journals were identified, with the highest impact factor being 20.1. 13 countries were identified, with the US contributing the most articles (approximately 70%). Regarding genes of investigation, VEGF was one of the early genes investigated, while more interested in RAS/MAPK has been garnered since 2015. There is a growing interest in AVM genomics and pathogenesis research. While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.

The 2-by-2 Inch "Key Window" in the Upper Extremity: An Anatomical Appraisal of the Accessibility and Proximity of the Major Nerves and Vessels.

BACKGROUND: The brachial plexus is a network of nerves located between the neck and axilla, which receives input from C5-T1. Distally, the nerves and blood vessels that supply the arm and forearm form a medial neurovascular bundle. The purpose of this study was to illustrate that a peripheral nerve dissection via a 2 × 2 inch window would allow for identification and isolation of the major nerves and blood vessels that supply the arm and forearm. METHODS: A right side formalin-fixed latex-injected cadaveric arm was transected at the proximal part of the axillary fold and included the scapular attachments. Step-by-step anatomical dissection was carried out and documented with three-dimensional digital imaging. RESULTS: A 2 × 2 inch window centered 2 inches distal to the axillary fold on the medial surface of the arm enabled access to the major neurovascular structures of the arm and forearm: the median nerve, ulnar nerve, medial antebrachial cutaneous nerve, radial nerve and triceps motor branches, musculocutaneous nerve and its biceps and brachialis branches and lateral antebrachial cutaneous nerve, basilic vein and brachial artery and vein, and profunda brachii artery. CONCLUSIONS: Our study demonstrates that the majority of the neurovascular supply in the arm and forearm can be accessed through a 2 × 2 inch area in the medial arm. Although this "key window" may not be entirely utilized in the operative setting, our comprehensive didactic description of peripheral nerve dissection in the cadaver laboratory can help in safer identification of complex anatomy encountered during surgical procedures.

Patterns of recurrence and disease progression in patients with positive-margin olfactory neuroblastoma following primary resection.

OBJECTIVE: Olfactory neuroblastoma (ONB) is a rare, malignant tumor of the sinonasal tract that arises from olfactory epithelium. Although surgery is the preferred first-line treatment, tumor involvement of adjacent structures may preclude the ability to achieve negative margins during initial resection. Herein, the authors examine the oncological outcomes of patients with positive margins after primary resection of ONB, with the aim of determining predictors of disease progression and patterns of recurrence. METHODS: The authors performed an institutional review of 25 patients with positive-margin ONB after resection. Cox survival analyses were used to determine any statistically significant predictors of worse progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 93 patients who were diagnosed with ONB were identified, of whom 25 patients had positive margins following their primary resection. Eleven (44%) had a delayed finding of positive margins that were initially negative in the operating room but returned as positive on final pathology. Four patients had subtotal resection (STR), whereas the remaining patients underwent gross-total resection. Twenty-four patients received adjuvant radiotherapy (96%), and 15 additionally received adjuvant chemotherapy (60%). Fourteen patients (56%) experienced recurrence/progression at a median time of 35 months following resection (IQR 19-70 months). Local recurrence occurred in 10 patients (40%), regional in 9 (36%), and distant metastasis in 2 (8%). In Cox survival analyses, the 5-year PFS and OS were 55.1% and 79.2%, respectively. Kadish stage D was predictive of worse PFS in univariate (hazard ratio [HR] 15.67, 95% CI 3.38-72.61, p < 0.001) and multivariate (HR 15.46, 95% CI 1.45-164.91, p = 0.023) analyses. Hyams grade, adjuvant chemotherapy, and primary radiotherapy were not associated with PFS. Furthermore, Kadish stage D and STR were predictive of worse OS in univariate analysis (HR 12.64, 95% CI 2.03-78.86, p = 0.007; HR 7.31, 95% CI 1.45-36.84, p = 0.016; respectively). However, local and regional recurrence was not associated with worse OS. CONCLUSIONS: Approximately half of patients with positive-margin ONB may experience disease recurrence. Patients with an advanced disease stage (Kadish D) may have a higher likelihood of developing recurrence/progression. Furthermore, patients with tumor burden following resection (STR and Kadish D) may have worse OS. However, in positive-margin ONB with no gross disease following initial resection, the presence of disease recurrence does not significantly alter survival when receiving salvage therapy.

Safety of the immediate use of nonsteroidal anti-inflammatory drugs after adult craniotomy for tumor.

OBJECTIVE: Poor pain control has a negative impact on postoperative recovery and patient satisfaction. However, overzealous pain management, particularly with opioids, can confound serial neurological assessments, increase morbidity, and predispose patients to long-term dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating postoperative pain and can limit opioid intake, but their use has been limited in patients undergoing craniotomy for brain tumor resection due to concerns of an increased hemorrhage risk. Herein, the authors aim to 1) address the safety of NSAID use in the immediate postoperative setting and 2) determine whether NSAID administration decreases opioid use following craniotomy for tumor resection in adult patients. METHODS: The authors conducted a retrospective cohort study of patients 18 years and older with an estimated glomerular filtration rate ≥ 60 ml/min/body surface area who had undergone craniotomy for tumor resection at their institution between 2019 and 2021. NSAID use in the first 48 hours following surgery was recorded. Primary outcomes were postoperative hemorrhage requiring a return to the operating room before hospital discharge and within 30 days of surgery. Secondary outcomes were more-than-minimal hemorrhage that did not require reoperation, acute kidney injury, and total opioid use within 48 hours after craniotomy. RESULTS: Among 1765 reviewed patient records, 1182 were eligible for inclusion in this analysis. Amid these records were 114 patients (9.6%) who had received at least one dose of an NSAID within 48 hours of their craniotomy. Four (0.3%) patients experienced bleeding requiring a return to operating room, one of whom was from the NSAID-treated group (RR 3.12, 95% CI 0.33-29.77, p = 0.30). No significant difference in nonoperative intracranial hemorrhage (RR 1.34, 95% CI 0.54-3.35, p = 0.53), postoperative acute kidney injury, or clinically significant extracranial bleeding was found between the NSAID and no-NSAID groups. Patients in the NSAID group had significantly higher oral morphine equivalent use (median 68 vs 30, p < 0.001). CONCLUSIONS: Postoperative NSAID use following craniotomy for tumor resection was not associated with an increased risk of hemorrhage requiring a return to the operating room. The authors noted higher opioid use in the patients treated with NSAIDs, which may reflect underlying reasons for the decision to treat patients with NSAIDs in the immediate postoperative period. These data warrant further investigation of NSAIDs as a safe, opioid-sparing postoperative pain management strategy in patients with normal kidney function who are undergoing intracranial tumor resection.

The Mayo, Cushing, and Osler Influence on A. L. Rhoton: A Historical Vignette of the Interconnectedness Between Highly Influential Neurosurgery Leaders over 100 Years.

The careers of the Mayo brothers, Harvey Cushing, and Sir William Osler greatly shaped medical and surgical practice in the late 19th century and early 20th century and created a legacy to influence decades of physicians to follow. Additionally, these individuals were instrumental in the founding of neurosurgery as a distinct surgical specialty. Alongside these great men, Dr. Albert L. Rhoton Jr., revolutionized neurosurgical practice through his study of neuroanatomy and development of microsurgical technique in the second half of the 20th century. This review of the interactions and relationships between the Mayo brothers, Cushing, and Osler and their influences on Rhoton highlights the 100-year-long interconnectedness shared between these giants in the history of neurosurgery.

Association of sarcopenia with oncologic outcomes of primary treatment among patients with oral cavity cancer: A systematic review and meta-analysis.

GOAL: We performed a systematic review of the literature and meta-analysis to determine how radiographic sarcopenia assessment methods and the presence of pre-treatment sarcopenia impact oncologic outcomes in patients with oral cavity cancer. INTRODUCTION: Pre-treatment sarcopenia has been associated with poor outcomes in many different malignancies, including head and neck cancers. However, the impact sarcopenia has on outcomes for oral cavity cancer patients is not well understood. RESULTS: Twelve studies met our inclusion criteria, totaling 1007 patients. 359 (36%) of these patients were reported as sarcopenic. The most commonly utilized sarcopenia assessment methods were L3 skeletal muscle index (n = 5) and C3 skeletal muscle index to estimate L3 skeletal muscle index (n = 5). The majority of studies established their sarcopenia cutoffs as the lowest quartile skeletal muscle index in their patient cohorts. Five studies were included in our meta-analysis, totaling 251 sarcopenic and 537 non-sarcopenic patients. Compared to non-sarcopenic patients, sarcopenic patients were found to have significantly poorer overall survival (univariate: HR = 2.24, 95% CI: 1.71-2.93, I2 = 0%; multivariate: HR = 1.93, 95% CI: 1.47-2.52, I2 = 0%) and disease-free survival (univariate: HR = 2.10, 95% CI: 1.50-2.92, I2 = 0%; multivariate: HR = 1.79, 95% CI: 1.29-2.47, I2 = 10%). CONCLUSIONS: Over one-third of oral cavity cancer patients may present with sarcopenia. Pre-treatment sarcopenia is associated with significantly worse overall and disease-free survival.

Embolization of Large and Giant Posterior Fossa Hemangioblastomas: The Experience of a Single Tertiary Care Center.

Background Hemangioblastomas pose an inherent surgical risk due to the potential for high intraoperative blood loss, especially in larger tumors. One approach to minimize this risk is to use preoperative embolization. Herein, we present our institutional experience treating large and giant cerebellar hemangioblastomas. Methods We performed a retrospective chart review of 19 patients with cerebellar hemangioblastomas that had a maximal diameter of >3 cm. We performed a literature review and included individual patient-level data that met our >3 cm diameter cerebellar hemangioblastoma inclusion criteria. Results Our cohort consisted of 19 patients that received a total of 20 resections for their cerebellar hemangioblastomas. Preoperative embolization was utilized in eight cases (38.1%). One patient experienced transient neurological complications after embolization (12.5%). Tumors of patients in the embolization group had larger median total, solid, and cystic volumes and were more likely to involve the cerebellopontine angle than those in the non-embolized group. Compared with non-embolized patients, embolized patients had less decrease in their hemoglobin, lower volumes of estimated blood loss, reduced rates of postoperative complications and permanent deficits, and greater instances of neurological improvement. The larger cohort (obtained from the combining our cohort with patients identified during a literature review) consisted of 99 patients with 39 receiving preoperative embolization. Conclusion It is important to examine individual patient characteristics when determining eligibility for preoperative embolization. However, improvements in endovascular techniques have made preoperative embolization a safe and effective procedure with minimal risks that can be performed in many patients.

The longitudinal risk of hemorrhage of melanoma brain metastases after Gamma Knife radiosurgery.

OBJECTIVE: The objective of this study was to analyze the hemorrhagic risk of melanoma brain metastases after Gamma Knife radiosurgery (GKRS). METHODS: A prospective institutional database was retrospectively queried to identify patients who underwent GKRS for melanoma brain metastases between 1990 and 2021. Lesional hemorrhage was defined as definite or possible based on radiologists' readings, and severity was graded according to Common Terminology Criteria for Adverse Events. RESULTS: Two hundred ninety-one patients with 1083 lesions treated in 419 sessions were identified. The mean (± SD) patient age was 60 ± 15 years, and 61% were male. The median follow-up period for overall survival (OS) was 11 (range 0-214) months with 581 patient-years. Definite/possible lesional hemorrhages occurred in 13% of lesions, with grade 3 hemorrhages observed in 4% of lesions. Surgical intervention was required in 2% of cases (5% of patients), and all resected lesions were pathologically consistent with melanoma. A decreased risk of definite/possible lesional hemorrhage was associated with a later time period between 2015 and 2021 (OR 0.45, 95% CI 0.266-0.75, p = 0.0021), increased marginal dose (OR 0.91, 95% CI 0.83-0.99, p = 0.037), antiplatelet use post-GKRS (OR 0.195, 95% CI 0.083-0.46, p < 0.001), and whole-brain radiotherapy (WBRT; OR 0.53, 95% CI 0.344-0.82, p = 0.0042). After 2015, more patients received anticoagulation, B-Raf proto-oncogene inhibitors, and immune checkpoint inhibitors, and fewer received bevacizumab (p < 0.001). The cumulative risk of lesional hemorrhage was 17%-20% at 36 months from GKRS, with 95%-96% of cases occurring within 12 months. The median patient OS was 11 (95% CI 9-13) months, and multivariate Cox regression analysis revealed that antiplatelet agents (hazard ratio [HR] 0.66, 95% CI 0.45-0.96, p = 0.031) and immune checkpoint inhibitors (HR 0.35, 95% CI 0.26-0.48, p < 0.001) were associated with longer OS, while WBRT (HR 1.36, 95% CI 1.02-1.81, p = 0.037) and definite/possible hemorrhage (HR 1.39, 95% CI 1.04-1.85, p = 0.024) were associated with shorter OS. CONCLUSIONS: The definite hemorrhage risk of melanoma brain metastases after GKRS was 17% in the first 3 years and 95% of the lesional hemorrhage occurred within the 1st year. Surgical intervention was needed in 5% of patients. Antiplatelet agents and immune checkpoint inhibitors were associated with improved OS, while definite/possible hemorrhage was associated with worse OS.

Lower Cranial Nerve Schwannomas: Cohort Study and Systematic Review.

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

Association of moyamoya vasculopathy with autoimmune disease: a systematic review and pooled analysis.

Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.

The utility of PET for detecting corticotropinomas in Cushing disease: a scoping review.

While magnetic resonance imaging (MRI) is the current standard imaging method for diagnosing and localizing corticotropinomas in Cushing disease, it can fail to detect adenomas in up to 40% of cases. Recently, positron emission tomography (PET) has shown promise as a diagnostic tool to detect pituitary adenomas in Cushing disease. We perform a scoping review to characterize the uses of PET in diagnosing Cushing disease, with a focus on describing the types of PET investigated and defining PET-positive disease. A scoping review was conducted following the PRISMA-ScR guidelines. Thirty-one studies fulfilled our inclusion criteria, consisting of 10 prospective studies, 8 retrospective studies, 11 case reports, and 2 illustrative cases with a total of 262 patients identified. The most commonly utilized PET modalities in prospective/retrospective studies were FDG PET (n = 5), MET PET (n = 5), 68 Ga-DOTATATE PET (n = 2), 13N-ammonia PET (n = 2), and 68 Ga-DOTA-CRH PET (n = 2). MRI positivity ranged from 13 to 100%, while PET positivity ranged from 36 to 100%. In MRI-negative disease, PET positivity ranged from 0 to 100%. Five studies reported the sensitivity and specificity of PET, which ranged from 36 to 100% and 50 to 100%, respectively. PET shows promise in detecting corticotropinomas in Cushing disease, including MRI-negative disease. MET PET has been highly investigated and has demonstrated excellent sensitivity and specificity. However, preliminary studies with FET PET and 68 Ga-DOTA-CRH PET show promise for achieving high sensitivity and specificity and warrant further investigation.

Predicting disease progression and the need for tumor-directed treatment in tectal plate gliomas.

OBJECTIVE: Tectal plate gliomas are rare, slow-growing tumors of the midbrain that are discovered predominantly in the pediatric population. Because of their indolent nature, treatment mainly consists of observation and management of hydrocephalus. Unfortunately, a subset of tectal gliomas may exhibit tumor enlargement and disease progression. Currently, there are no established guidelines for predicting future progression of tectal gliomas or the need for tumor-directed treatment. In this paper, the authors present a large case series of tectal plate gliomas with the aim of determining early indicators of tumor progression and the need for tumor-directed treatment in a pediatric population, along with providing their experience in treating progressive tumors. METHODS: A retrospective chart review of 170 patients diagnosed with tectal plate glioma from a single institution, of whom 67 were pediatric patients (≤ 18 years of age), was performed. Univariate analysis was used to determine statistically significant predictors of symptomatic disease progression requiring eventual tumor-directed therapy. RESULTS: The median patient age of the full cohort was 24 years (range 0-73 years). Compared with the pediatric population, the adult population had more instances of incidental lesions (p < 0.001) and lower rates of hydrocephalus (50% vs 84%, p < 0.001). Of the pediatric patients who had ≥ 5 years of follow-up (n = 51), 12 (24%) experienced radiological progression and 13 (25%) required treatment for their tumor. The 1-year, 5-year, and 10-year radiographic progression-free survival (PFS) rates were 98%, 90%, and 86%, respectively. In univariate analysis, lesion involvement of the pons, moderate T1 hypointensity, and moderate contrast enhancement on baseline radiology were significantly associated with worse radiographic PFS. Alternatively, significant predictors of requiring tumor-directed treatment included extraocular eye movement abnormalities at presentation, involvement of the lesion beyond the tectum on baseline radiology, moderate T1 hypointensity, moderate contrast enhancement, and an increase in total lesion size during progression. At the most recent follow-up, 94% of the patients had stable/nonprogressive disease, 2% had progressive disease, and 4% died of tumor progression. CONCLUSIONS: Patients who demonstrate radiographic progression may not necessarily experience clinical/symptomatic progression or require tumor-directed treatment. Certain patient presentation characteristics and baseline radiographic features may be predictive of worse radiographic PFS or the need for future tumor-directed treatment in the pediatric population. Typically, the natural history of these lesions lends to excellent long-term survival, even in patients who experience clinical progression, should appropriate treatment be initiated.

Bone morphogenetic proteins in spine surgery: a scientometric analysis to date.

OBJECTIVE: Bone morphogenetic proteins (BMPs) are part of the transforming growth factor-beta superfamily and are involved in bone formation and repair. In spine surgery, recombinant human BMP (rhBMP) is used as an alternative to autografts for spinal fusions. This study aimed to evaluate bibliometric parameters and citations of the literature on BMPs to provide an overview of how the field has evolved. METHODS: A comprehensive search of the literature was conducted using Elsevier's Scopus database to capture all the published and indexed studies relevant to BMPs from 1955 to the present. A discrete set of validated bibliometric parameters was extracted and analyzed. All statistical analyses were performed using R 4.1.1. RESULTS: The 100 most cited articles were published between 1994 and 2018 by 472 unique authors in 40 sources (e.g., journals and books). On average, there were 279 citations per publication and 17.69 citations per publication per year. The United States had the publications with the most citations (n = 23,761), followed by Hong Kong (n = 580) and the United Kingdom (n = 490). The three institutions in the United States with the greatest number of publications in the field were Emory University (n = 14), Hughston Clinic (n = 9), Hospital for Special Surgery (n = 6), and University of California (n = 6). CONCLUSIONS: The authors evaluated and characterized the 100 most cited articles about BMP. Most of the publications were clinical in nature and focused on BMP's application in spine surgery. While early scientific efforts focused on basic science research to advance the understanding of BMP's mechanism of action in promoting bone formation, the majority of the more recent publications are clinically focused. It will be beneficial to conduct more controlled clinical trials to compare the outcomes of BMP use with other methods.

Advancements and Technical Considerations for Extracellular Vesicle Isolation and Biomarker Identification in Glioblastoma.

Extracellular vesicles (EVs) are membrane-bound particles released by all cells. Previous research has found that these microscopic vesicles contribute to intercellular signaling and communication. EVs carry a variety of cargo, including nucleic acids, proteins, metabolites, and lipids. The composition of EVs varies based on cell of origin. Therefore, EVs can serve as an important biomarker in the diagnosis and treatment of various cancers. EVs derived from glioblastoma (GBM) cells carry biomarkers, which could serve as the basis for a potential diagnostic strategy known as liquid biopsy. Multiple EV isolation techniques exist, including ultrafiltration, size exclusion chromatography, flow field-flow fractionation, sequential filtration, differential ultracentrifugation, and density-gradient ultracentrifugation. Recent and ongoing work aims to identify cellular markers to distinguish GBM-derived EVs from those released by noncancerous cells. Strategies include proteomic analysis of GBM EVs, identification of GBM-specific metabolites, and use of Food and Drug Administration-approved 5-aminolevulinic acid-an oral agent that causes fluorescence of GBM cells-to recognize GBM EVs in a patient's blood. In addition, accurately and precisely monitoring changes in EV cargo concentrations could help differentiate between pseudoprogression and GBM recurrence, thus preventing unnecessary surgical interventions.

Selective denervation for cervical dystonia.

Cervical dystonia (spasmodic torticollis) is a condition that involves sustained, involuntary contraction of neck and shoulder muscles, leading to abnormal movements and head posture. The authors present the case of a 41-year-old man with severe right rotational torticollis for 1.5 years due to predominant right cervical paraspinal and left sternocleidomastoid muscle hyperactivity. Following failed medical management, the patient elected to undergo surgical treatment for his torticollis. In their video, the authors discuss the steps of selective denervation using a modified Bertrand procedure, highlighting the associated anatomy and surgical planes. At the 1.5-year follow-up, the patient had no pain and his head position remained straight. The video can be found here: https://stream.cadmore.media/r10.3171/2022.9.FOCVID2291.

The LazyBox Educational Intervention Trial: Can Longitudinal Practice on a Low-Fidelity Microsurgery Simulator Improve Microsurgical Skills?

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

Strategies, considerations, and recent advancements in the development of liquid biopsy for glioblastoma: a step towards individualized medicine in glioblastoma.

OBJECTIVE: Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle-based liquid biopsy targeting nonneoplastic extracellular vesicles. METHODS: The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance. RESULTS: Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM. CONCLUSIONS: Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon's arsenal in the near future for the treatment and management of GBM patients.