Comparative Analysis of Antithrombotic Therapy Outcomes in Mild Traumatic Brain-Injury Patients: A Focus on Bleeding Risk and Hospital-Stay Duration.

BACKGROUND: Traumatic brain injury (TBI) in the elderly is a noteworthy pathology due to the exponential increase in population age, and the effects of antiplatelet and anticoagulation on patients' outcomes are still a matter of dispute. The aim of the present study was to evaluate the impact of various antithrombotic agents on patients with mild TBI, focusing on the risk of intracranial bleeding (ICH) and length of hospitalization (LOS). METHODS: A retrospective analysis was conducted, including patients with a diagnosis of TBI admitted to the Emergency Department between 2021 and 2022. Patients were classified according to the concurrent antithrombotic therapy as aspirin (ASA), antiplatelets, direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH). The primary outcome was the ICH occurrence, while the secondary outcome was the LOS. The statistical analysis was performed via logistic regression models in R and STATA 13.1 software. Fisher's exact test was used for the statistical significance. RESULTS: 267 patients with mild TBI were included; 148 were not on antithrombotic agents, 43 were on aspirin, 33 on DOACs, 5 on LMWH, 22 on antiplatelets, and 16 on VKA. Out of the total, 9 patients experienced ICH, none of which were on DOACs, LMWH, or VKA, but 4-out of 65-were on antiplatelets, and 5-out of 148-were not on antithrombotic therapies. Patients not on antithrombotic therapy had the shortest LOS at 0.46 days, while those on VKA had the longest LOS at 1.19 days; similar trends were observed for patients on DOAC and LMWH. CONCLUSIONS: The results reveal that TBI patients on anticoagulants/antiplatelets had longer hospital stays compared with those on aspirin alone. Notably, VKA was the strongest predictor for an extended LOS. Regarding ICH, patients taking only aspirin were twice as likely to experience bleeding compared with those on anticoagulants/antiplatelets. However, to achieve statistically significant evidence, further research with a larger cohort of patients is needed.

Supracerebellar "Flyover" Approach to Dumbbell Falcotentorial Meningioma Encasing the Galenic Venous System.

Falcotentorial meningiomas involve the tentorial apex and straight sinus, posing challenges when encasing the galenic venous system.1 Microneurosurgery is considered the best treatment option for large falcotentorial meningiomas because it provides a definitive cure.2 In contrast, Gamma Knife surgery mainly allows the control of smaller or residual tumors after microsurgical resection.3 Approach selection between interhemispheric supratentorial versa supracerebellar transtentorial is dictated by the displacement of the Galen vein.1,4-8Video 1 describes the critical surgical steps of the supracerebellar "flyover" approach for a Bassiouni type II dumbbell falcotentorial meningiomas encasing the galenic venous system. Preoperative embolization was ruled out due to potential additional morbidity and mortality risks.9,10 A perimedian supracerebellar infratentorial transtentorial approach was performed with the patient in ¾ prone Concorde position. After early devascularization and division of the tentorium, the meningioma was internally debulked while preserving the arachnoid plane. The posterior choroidal arteries, internal cerebral veins, basal veins of Rosenthal, and vein of Galen were carefully dissected, and the tumor was completely resected. The patient was discharged on postoperative day 3 with no deficits. Postoperative magnetic resonance imaging confirmed a Simpson grade 1 resection. Pathology revealed a grade 2 meningioma. The patient remained asymptomatic with no recurrence at a 10-year follow-up. The reported case demonstrates that the most critical factor in the choice of approach to midline dumbbell falcotentorial meningiomas is the relationship of the tumor to the galenic venous system and its tributaries.

Comparative Analysis of Surgical Working Corridors for Meckel Cave Trigeminal Schwannomas: A Quantitative Anatomic Study.

BACKGROUND AND OBJECTIVES: Volumetric analysis of the working corridors of the interdural approach to the Meckel cave may lead to a selection of routes which are anatomically more advantageous for trigeminal schwannoma resection. The herein-reported anatomic study quantitively compares the infratrochlear (IT) transcavernous, anteromedial (AM), and anterolateral (AL) corridors, highlighting their feasibility, indications, advantages, and limitations. METHODS: Anatomic boundaries and depth of Meckel cave, porus trigeminus, IT transcavernous, AM, and AL corridors were identified in 20 formalin-fixed latex-injected cadaveric heads and were subsequently measured. The corridor areas and volumes were derived accordingly. Each opening angle was also calculated. Angles and volumes were compared using analysis of variance. Statistical significance was set at a P -value <.05. RESULTS: The IT transcavernous corridor volume was greater than that of the AM and AL. The opening angle of the AM middle fossa triangle was wider than the other 2. CONCLUSION: The IT corridor can be advantageous for Meckel cave schwannomas invading the cavernous sinus and those with a notable extension into the posterior fossa because the transcavernous approach maximizes the working space into the retrosellar area. The AM middle fossa corridor is strategic in schwannomas confined to the Meckel cave with a minor extension into the posterior fossa. It raises the chance of total resection with a single approach involving the porus trigeminus opening.

Photo-Stacking Technique for Neuroanatomical High-Definition Photography and 3-Dimensional Modeling.

BACKGROUND: Three-dimensional (3D) neuroanatomical knowledge is vital in neurosurgery. Technological advances improved 3D anatomical perception, but they are usually expensive and not widely available. The aim of the present study was to provide a detailed description of the photo-stacking technique for high-resolution neuroanatomical photography and 3D modeling. METHODS: The photo-stacking technique was described in a step-by-step approach. The time for image acquisition, file conversion, processing, and final production was measured using 2 processing methods. The total number and file size of images are presented. Measures of central tendency and dispersion report the measured values. RESULTS: Ten models were used in both methods achieving 20 models with high-definition images. The mean number of acquired images was 40.6 (14-67), image acquisition time 51.50 ± 18.8 s, file conversion time 250 ± 134.6 s, processing time 50.46 ± 21.46 s and 41.97 ± 20.84 s, and 3D reconstruction time was 4.29 ± 0.74 s and 3.89 ± 0.60 s for methods B and C, respectively. The mean file size of RAW files is 1010 ± 452 megabyte (MB) and 101.06 ± 38.09 MB for Joint Photographic Experts Group files after conversion. The mean size of the final image means size is 71.9 ± 0.126 MB, and the mean file size of the 3D model means is 37.4 ± 0.516 MB for both methods. The total equipment used was less expensive than other reported systems. CONCLUSIONS: The photo-stacking technique is a simple and inexpensive method to create 3D models and high-definition images that could prove valuable in neuroanatomy training.

The Party Wall: Redefining the Indications of Transcranial Approaches for Giant Pituitary Adenomas in Endoscopic Era.

The evolution of endoscopic trans-sphenoidal surgery raises the question of the role of transcranial surgery for pituitary tumors, particularly with the effectiveness of adjunct irradiation. This narrative review aims to redefine the current indications for the transcranial approaches for giant pituitary adenomas in the endoscopic era. A critical appraisal of the personal series of the senior author (O.A.-M.) was performed to characterize the patient factors and the tumor's pathological anatomy features that endorse a cranial approach. Traditional indications for transcranial approaches include the absent pneumatization of the sphenoid sinus; kissing/ectatic internal carotid arteries; reduced dimensions of the sella; lateral invasion of the cavernous sinus lateral to the carotid artery; dumbbell-shaped tumors caused by severe diaphragm constriction; fibrous/calcified tumor consistency; wide supra-, para-, and retrosellar extension; arterial encasement; brain invasion; coexisting cerebral aneurysms; and separate coexisting pathologies of the sphenoid sinus, especially infections. Residual/recurrent tumors and postoperative pituitary apoplexy after trans-sphenoidal surgery require individualized considerations. Transcranial approaches still have a critical role in giant and complex pituitary adenomas with wide intracranial extension, brain parenchymal involvement, and the encasement of neurovascular structures.

Surgical management of symptomatic hemangioma of the geniculate ganglion: fascicular-sparing resection or grafting?

Geniculate ganglion hemangioma (GGH) is rarely presented in the neurosurgical literature. It extends extradurally on the middle fossa floor and displaces the intratemporal part of the facial nerve. Surgical treatment is advisable at early symptoms. Proposed techniques include fascicular-sparing resection or nerve interruption with grafting. No definitive conclusions exist about the superiority of a certain technique in preserving facial nerve integrity and function. Through the description of a surgically managed symptomatic GGH, we herein discuss literature data about the surgical results of fascicular-sparing resection versus grafting. A PRISMA-based literature search was performed on the PubMed database. Only articles in English and published since 1990 were selected and furtherly filtered based on the best relevance. Statistical comparisons were performed with ANOVA. One hundred sixteen GGHs were collected, 56 were treated by fascicular-sparing resection, and 60 were treated by grafting. The facial function was improved, or unchanged, in 53 patients of the fascicular-sparing group and 30 patients of the grafting one. Sixty-five patients achieved a good (House-Brackmann (HB) grade III) postoperative facial outcome, of which 47 and 18 belonged to the fascicular-sparing and grafting group, respectively. Greater efficacy of the fascicular-sparing technique in the achievement of a better facial outcome was found (p = 0.0014; p = 0.0022). A surgical resection at the earliest symptoms is critical to preserve the facial nerve function in GGHs. Fascicular-sparing resection should be pursued in symptomatic cases with residual facial function (I-III HB). Conversely, grafting has a rationale for higher HB grades (V-VI). Broader studies are required to confirm these findings and turn them into new therapeutic perspectives.

Surgical management of thoracolumbar junction fractures: An evidence-based algorithm.

Background: The management of thoracolumbar junction (TLJ) fractures, involving the restoring anatomical stability and biomechanics properties, still remains a challenge for neurosurgeons.Despite the high frequency of these injuries, specific treatment guidelines, set on biomechanical properties, have not yet been assumed. The present study is meant to propose an evidence-based treatment algorithm. The primary aim for the protocol validation was the assessment of postoperative neurological recovery. The secondary objectives concerned the evaluation of residual deformity and rate of hardware failure. Technical nuances of surgical approaches and drawbacks were further discussed. Methods: Clinical and biomechanical data of patients harboring a single TLJ fracture, surgically managed between 2015 and 2020, were collected. Patients' cohorts were ranked into 4 groups according to Magerl's Type, McCormack Score, Vaccaro PLC point, Canal encroachment, and Farcy Sagittal Index. The outcome measures were the early/late Benzel-Larson Grade and postoperative kyphosis degree to estimate neurological status and residual deformity, respectively. Results: 32 patients were retrieved, 7, 9, 8, and 8 included within group 1, 2, 3, and 4, respectively. Overall neurological outcomes significantly improved for all patients at every follow-up stage (p â€‹< â€‹0.0001). Surgeries gained a complete restoration of post-traumatic kyphosis in the entire cohort (p â€‹< â€‹0.0001), except for group 4 which experienced a later worsening of residual deformity. Conclusions: The choice of the most appropriate surgical approach for TLJ fractures is dictated by morphological and biomechanical characteristics of fracture and the grade of neurological involvement. The proposed surgical management protocol was reliable and effective, although further validations are needed.

Fascicular-Sparing Technique for Resection of Cerebellopontine Angle Facial Nerve Schwannoma.

Surgery of cerebellopontine angle (CPA) facial nerve schwannoma (FNS) in patients with good facial nerve function is a challenge.1-10Video 1 highlights the fascicular-sparing technique for resection of a CPA FNS. A 41-year-old male patient symptomatic with persistent headaches and tinnitus underwent a retrosigmoid approach for a right cystic CPA tumor, presumed vestibular schwannoma. Intraoperatively, the facial nerve was identified as fine multiple strands splayed around the perimetry of the tumor, which elicited a motor response at a low threshold stimulation. This finding led to the intraoperative diagnosis of FNS according to the reported criteria.5 Neuromonitoring-assisted fascicular-sparing resection technique was performed. It involved the gradual separation of the uninvolved nerve fibers using a fine-stimulating dissector at a threshold of 0.2 mA. Entry into the tumor was at a stimulation silent cyst. The tumor was debulked with preservation of the endoneurium and pulse irrigation hemostasis. A near-total resection was performed. The patient was discharged on the second postoperative day with a House-Brackman III facial nerve deficit. The deficit remained stable during the following annual follow-up visits. Resection of CPA FNS is indicated at the earliest sign of deficit. However, it might be encountered as masquerading at the surgery of an acoustic tumor. The fascicular-sparing technique is critical in avoiding injuries to the endoneurium during the resection and with the ability to preserve function. The sparing of endoneurium avoids collagenization, fibrosis, and ischemia of the nerve, which are known to be the pathologic substrate of worse functional outcomes.

Optic Foraminotomy versus Anterior Clinoidectomy for Small Superior-Projecting Paraclinoid Aneurysms: Visual and Angiographic Outcome Evaluation.

INTRODUCTION: Optic foraminotomy (OF) has been recently proposed as an alternative to anterior clinoidectomy (AC) for selected types of paraclinoid aneurysms. In this study, OF and AC were compared for small superior-projecting paraclinoid aneurysms assuming visual and angiographic results as outcome measures. Indications for OF are also discussed. METHODS: Data of patients who underwent surgery for a paraclinoid aneurysm in the last 10 years were collected across 3 tertiary hospitals. Small to regular-size and superior projecting aneurysms were sorted. Multiple and complex aneurysms were excluded. Records of patients who went through OF were compared with those of patients who underwent AC. Neurologic outcome was reported as a modified Rankin Scale. Aneurysm complete occlusion rate and rate of approach-related worsened vision were selected as outcome measures of efficacy and safety, respectively, of the OF versus AC. Unpaired t test and χ2 test were used for numerical and categorical variables, respectively. A P value less than 0.05 was considered statistically significant. RESULTS: OF and AC groups involved 18 and 25 patients, respectively. Complication rate, overall neurologic outcome, rate of approach-related worsened vision, and complete occlusion rate did not differ between the groups. The average follow-up was 51 ± 34 and 60 ± 41 months in the OF and AC groups, respectively. CONCLUSIONS: Compared to AC, OF did not show either a higher rate of approach-related worsened vision or a lower aneurysm complete occlusion rate. OF can be considered a valid alternative to the AC for small superior-projecting dorsal ICA wall paraclinoid aneurysms.

Brain AVMs-Related microRNAs: Machine Learning Algorithm for Expression Profiles of Target Genes.

INTRODUCTION: microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs. METHODS: A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: "brain arteriovenous malformations", "cerebral arteriovenous malformations", "microRNA", and "miRNA". All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions. RESULTS: four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression. CONCLUSION: miRNAs expression appears to be critical in managing bAVMs' post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs.

Word2vec Word Embedding-Based Artificial Intelligence Model in the Triage of Patients with Suspected Diagnosis of Major Ischemic Stroke: A Feasibility Study.

BACKGROUND: The possible benefits of using semantic language models in the early diagnosis of major ischemic stroke (MIS) based on artificial intelligence (AI) are still underestimated. The present study strives to assay the feasibility of the word2vec word embedding-based model in decreasing the risk of false negatives during the triage of patients with suspected MIS in the emergency department (ED). METHODS: The main ICD-9 codes related to MIS were used for the 7-year retrospective data collection of patients managed at the ED with a suspected diagnosis of stroke. The data underwent "tokenization" and "lemmatization". The word2vec word-embedding algorithm was used for text data vectorization. RESULTS: Out of 648 MIS, the word2vec algorithm successfully identified 83.9% of them, with an area under the curve of 93.1%. CONCLUSIONS: Natural language processing (NLP)-based models in triage have the potential to improve the early detection of MIS and to actively support the clinical staff.

Microscope-based augmented reality with diffusion tensor imaging and fluorescein in insular glioma resection.

Maximal safe resection is the goal of insular glioma surgery. The combination of intraoperative augmented reality (AR) diffusion tensor imaging (DTI) fiber tracking with fluorescein dye (F) helps achieve this goal throughout a microscope-based visualization of the tumor and white matter fiber tracts. The aim of the present video article was to show the technical key aspects of DTI-F microscope-based AR-assisted surgery during the gross-total resection of an insular Berger-Sanai type I+IV high-grade glioma in a 63-year-old patient, performed through a pterional transsylvian approach. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID2157.

Emerging immune-based technologies for high-grade gliomas.

INTRODUCTION: The selection of a tailored and successful strategy for high-grade gliomas (HGGs) treatment is still a concern. The abundance of aberrant mutations within the heterogenic genetic landscape of glioblastoma strongly influences cell expansion, proliferation, and therapeutic resistance. Identification of immune evasion pathways opens the way to novel immune-based strategies. This review intends to explore the emerging immunotherapies for HGGs. The immunosuppressive mechanisms related to the tumor microenvironment and future perspectives to overcome glioma immunity barriers are also debated. AREAS COVERED: An extensive literature review was performed on the PubMed/Medline and ClinicalTrials.gov databases. Only highly relevant articles in English and published in the last 20 years were selected. Data about immunotherapies coming from preclinical and clinical trials were summarized. EXPERT OPINION: The overall level of evidence about the efficacy and safety of immunotherapies for HGGs is noteworthy. Monoclonal antibodies have been approved as second-line treatment, while peptide vaccines, viral gene strategies, and adoptive technologies proved to boost a vivid antitumor immunization. Malignant brain tumor-treating fields are ever-changing in the upcoming years. Constant refinements and development of new routes of drug administration will permit to design of novel immune-based treatment algorithms thus improving the overall survival.

Novel "T-Dimension" Therapies for Pediatric Optic Pathway Glioma: A Timely, Targeted, and Tailored Treatment Trend.

INTRODUCTION: Novel targeted and tailored therapies can substantially improve the prognosis for optic pathway glioma (OPG), especially when implemented in a timely manner. However, their tremendous potential remains underestimated. Therefore, in this study, we provide an updated overview of the clinical trials, current trends, and future perspectives for OPG's novel therapeutic strategies. METHODS: We completed an extensive literature review using the PubMed, MEDLINE, and ClinicalTrials.gov databases. We analyzed and reported the data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Thioguanine, procarbazine, lomustine, and vincristine/vinblastine, as well as cisplatin-etoposide, provided excellent results in advanced-phase trials. Selumetinib and trametinib, two oral MEK inhibitors, have been approved for recurrent or refractory OPGs in association with the angiogenetic inhibitor bevacizumab. Among the mTOR inhibitors, everolimus and sirolimus showed the best results. Stereotactic radiosurgery and proton beam radiation therapy have advantages over conventional radiotherapy regimens. Timely treatment is imperative for acute visual symptoms with evidence of tumor progression. This latest evidence can help define a novel "T-Dimension" for pediatric OPG therapies. CONCLUSION: The novel "T-Dimension" for pediatric OPGs is based on recent evidence-based treatments, including combination chemotherapy regimens, molecular targeted therapies, stereotactic radiosurgery, and proton beam radiation therapy. Additional clinical trials are essential for validating each of these new therapies.

Immune Landscape in PTEN-Related Glioma Microenvironment: A Bioinformatic Analysis.

Introduction: PTEN gene mutations are frequently found in the genetic landscape of high-grade gliomas since they influence cell proliferation, proangiogenetic pathways, and antitumoral immune response. The present bioinformatics analysis explores the PTEN gene expression profile in HGGs as a prognostic factor for survival, especially focusing on the related immune microenvironment. The effects of PTEN mutation on the susceptibility to conventional chemotherapy were also investigated. Methods: Clinical and genetic data of GBMs and normal tissue samples were acquired from The Cancer Genome Atlas (TCGA)-GBM and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan−Meier survival curves were applied to estimate the overall survival (OS) and disease-free survival (DFS). The Genomics of Drug Sensitivity in Cancer platform was chosen to assess the response of PTEN-mutated GBMs to temozolomide (TMZ). p < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and PTEN status was assessed through Spearman's correlation analysis. Results: PTEN was found mutated in 22.2% of the 617 TCGA-GBMs patients, with a higher log2-transcriptome per million reads compared to the GTEx group (255 samples). Survival curves revealed a worse OS and DFS, albeit not significant, for the high-PTEN profile GBMs. Spearman's analysis of immune cells demonstrated a strong positive correlation between the PTEN status and infiltration of Treg (ρ = 0.179) and M2 macrophages (ρ = 0.303). The half-maximal inhibitor concentration of TMZ was proven to be lower for PTEN-mutated GBMs compared with PTEN wild-types. Conclusions: PTEN gene mutations prevail in GBMs and are strongly related to poor prognosis and least survival. The infiltrating immune lymphocytes Treg and M2 macrophages populate the glioma microenvironment and control the mechanisms of tumor progression, immune escape, and sensitivity to standard chemotherapy. Broader studies are required to confirm these findings and turn them into new therapeutic perspectives.

Far Lateral Approach.

The far lateral approach is an inferolateral extension of the lateral suboccipital approach. Designed for clipping of the aneurysms of the vertebrobasilar junction and proximal segments of the posterior inferior cerebellar artery, it became over the years a workhorse approach for ventral foramen magnum meningiomas and other intradural lesions located anterior to the dentate ligament.  This article summarizes the technical key aspects of the far lateral approach and transcondylar, supracondylar, and paracondylar extension.

Interhemispheric Approach.

The interhemispheric approach is the natural route to reach the parafalcine and paraventricular structures through the interhemispheric fissure. In this chapter, we report the main anterior and posterior corridors of the interhemispheric approach.

Cranio-Orbito-Zygomatic Approach.

The cranio-orbito-zygomatic (COZ) approach consists of an extension of the pterional approach characterized by the removal of the superolateral part of the orbital rim and zygoma. This key step tremendously increases the angular exposure to some deep targets and overall surgical freedom to the lesion. In this article we review the technical variations of the COZ approach, mainly focusing on the differential quantitative effects coming from the orbital osteotomy compared to the zygomatic one.