Advances in Anterolateral Approaches to the Lumbar Spine: A Focus on Technological Developments.

A historical overview of the evolution of anterolateral approaches to the lumber spine and associated patient outcomes is presented. In addition, the modern incorporation of new technologies is discussed, including interbody cages, intraoperative image guidance, robotics, augmented reality, and machine learning, which have significantly improved the spine surgery safety and efficacy profile. Current challenges and future directions are also covered, emphasizing the need for further research and development, particularly in robotic assistance and machine learning algorithms.

Topical tranexamic acid (TXA) is non-inferior to intravenous TXA in adult spine surgery: a meta-analysis.

Tranexamic acid (TXA) has long been utilized in spine surgery and can be administered through intravenous (IV) and topical routes. Although, topical and IV administration of TXA are both effective in decreasing blood loss during spine surgery, complications like deep vein thrombosis (DVT) and pulmonary embolism have been reported with the use of intravenous TXA (ivTXA). These potential complications may be mitigated through the use of topical TXA (tTXA). To assess optimal dosing protocols and efficacy of topical TXA in spine surgery, Embase, Ovid-MEDLINE, Scopus, Cochrane, and clinicaltrials.gov were queried for original research on the use of tTXA in adult patients undergoing spine surgery. Data parameters analyzed included blood loss, transfusion rate, thromboembolic, and other complications. Data was synthesized and confidence evaluated according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Nineteen studies were included in the final analysis with 2197 patients. Of the 18 published studies, 9 (50%) displayed high levels of evidence. Topical TXA showed a trend towards a lower risk of transfusion and complications. Protocols that used 1g tTXA showed a significantly reduced risk for transfusion when compared to controls (risk ratio -1.05, 95% CI (-1.62, -0.48); P = 0.94, I2 = 0%). Complications associated with tTXA included DVTs and wound infections. Topical TXA was non-inferior to intravenous TXA with similar efficacy and complication profiles for bleeding control in spine surgery; however, more studies are needed to discern benefits and risks.

Spatial Computing for preoperative planning and postoperative evaluation of single-position lateral approaches in spinal revision surgery.

Spatial computing (SC) in a surgical context offers reconstructed interactive four-dimensional models of radiological imaging. Preoperative and postoperative assessment with SC can offer more insight into personalized surgical approaches. Spine surgery has benefitted from the use of perioperative SC assessment. Herein, we describe the use of SC to perform a perioperative assessment of a revision spinal deformity surgery. A 79-year-old wheelchair-bound male presented to the neurosurgery clinic with a history of chronic lumbar pain associated with bilateral lower extremity weakness. His surgical history is significant for an L2-L5 lumbar decompression with posterior fixation 1 year prior. On examination, there were signs of thoracic myelopathy. Imaging revealed his previous instrumentation, pseudoarthrosis, and cord compression. We perform a two-staged operation to address the thoracic spinal cord compression and myelopathy, pseudoarthrosis, and malalignment with a lack of global spinal harmony. His imaging is driven by a spatial computing and SC environment and offers support for the diagnosis of his L2-3 and L4-5 pseudoarthrosis on the reconstructed SC-based computed tomography scan. SC enabled the assessment of the configuration of the psoas muscle and course of critical neurovascular structures in addition to graft sizing, trajectory and approach, evaluation of the configuration and durability of the anterior longitudinal ligament, and the overlying abdominal viscera. SC increases the familiarity of the patient's specific anatomy and enhances perioperative assessment. As such, SC can be used to preoperatively plan for spinal revision surgery.

Geographic Distribution in Training and Practice of Academic Neurological and Orthopedic Spine Surgeons in the United States.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: This study aimed to stratify the geographic distribution of academic spine surgeons in the United States, analyzing how this distribution highlights differences in academic, demographic, professional metrics, and gaps in access to spine care. METHODS: Spine surgeons were identified using American Association of Neurological Surgeons and American Academy of Orthopedic Surgeons databases, categorizing into geographic regions of training and practice. Departmental websites, National Institutes of Health (NIH) RePort Expenditures and Results, Google Patent, and NIH icite databases were queried for demographic and professional metrics. RESULTS: Academic spine surgeons (347 neurological; 314 orthopedic) are predominantly male (95%) and few have patents (23%) or NIH funding (4%). Regionally, the Northeast has the highest proportion per capita (3.28 surgeons per million), but California is the state with the highest proportion (13%). The Northeast has the greatest regional retention post-residency at 74%, followed by the Midwest (59%). The West and South are more associated with additional degrees. Neurosurgery-trained surgeons hold more additional degrees (17%) than orthopedic surgeons (8%), whereas more orthopedic surgeons hold leadership positions (34%) than neurosurgeons (20%). CONCLUSIONS: Academic spine surgeons are found at the highest proportion in the Northeast and California; the Northeast has the greatest regional retention. Spine neurosurgeons have more additional degrees, whereas spine orthopedic surgeons have more leadership positions. These results are relevant to training programs looking to correct geographic disparities, surgeons in search of training programs, or students in pursuit of spine surgery.

Removal of a Floating and Migrated Plate Screw in a Patient with a Failed Anterior Cervical Discectomy and Fusion.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure for degenerative cervical spine disease. Rare complications of ACDF surgery include hardware failure, in the form of screw loosening and migration, or rod breakage. We present a case in which we removed a migrated screw lodged in the esophagus from a patient with a failed anterior cervical fusion. OBJECTIVE: To present a surgical technique and considerations to remove a migrated screw. METHODS: The previous ACDF incision was reopened and exposure was gained under the guidance of a head and neck surgeon. Longus coli were mobilized off the spine bilaterally with electrocautery. After dissection, the screw was found lodged in the longitudinal muscle of the esophageal wall and excised with the use of a 15-blade. The integrity of the esophageal mucosa and submucosa was maintained and subsequently checked with rigid esophagoscopy. Fluoroscopy was used to confirm that all hardware was removed, with the exception of the anterior cages. RESULTS: The dislodged screw, which was embedded in the esophagus, was successfully removed. CONCLUSIONS: Failure of an ACDF carries a risk of screw migration, which may be asymptomatic even if the screw is lodged in the esophagus. Additional considerations are required with potential violations of the adjacent viscera.

Standard clinical approaches and emerging modalities for glioblastoma imaging.

Glioblastoma (GBM) is the most common primary adult intracranial malignancy and carries a dismal prognosis despite an aggressive multimodal treatment regimen that consists of surgical resection, radiation, and adjuvant chemotherapy. Radiographic evaluation, largely informed by magnetic resonance imaging (MRI), is a critical component of initial diagnosis, surgical planning, and post-treatment monitoring. However, conventional MRI does not provide information regarding tumor microvasculature, necrosis, or neoangiogenesis. In addition, traditional MRI imaging can be further confounded by treatment-related effects such as pseudoprogression, radiation necrosis, and/or pseudoresponse(s) that preclude clinicians from making fully informed decisions when structuring a therapeutic approach. A myriad of novel imaging modalities have been developed to address these deficits. Herein, we provide a clinically oriented review of standard techniques for imaging GBM and highlight emerging technologies utilized in disease characterization and therapeutic development.

Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas.

Glioblastoma multiforme (GBM) represents one of the most challenging malignancies due to many factors including invasiveness, heterogeneity, and an immunosuppressive microenvironment. Current treatment modalities have resulted in only modest effect on outcomes. The development of viral vectors for oncolytic immunovirotherapy and targeted drug delivery represents a promising therapeutic prospect for GBM and other brain tumors. A host of genetically engineered viruses, herpes simplex virus, poliovirus, measles, and others, have been described and are at various stages of clinical development. Herein we provide a review of the advances and current state of oncolytic virotherapy for the targeted treatment of GBM and malignant gliomas.

Cerebellar talcosis following posterior reversible encephalopathy syndrome in an intravenous methamphetamine abuser.

BACKGROUND: Intravenous (IV) methamphetamine abuse is associated with a variety of short- and long-term effects on the nervous system, some of which have yet to be fully elucidated. One known systemic complication that has not been described in nervous system tissues is the deposition of substrate crystals contained in injectable drugs. CASE DESCRIPTION: An unusual case is presented of a 35-year-old active IV methamphetamine abuser with posterior reversible encephalopathy syndrome (PRES) who subsequently developed multifocal bilateral cerebellar enhancing lesions and leptomeningeal enhancement due to biopsy-proven crystalline deposits. CONCLUSION: Although large crystalline substances will not normally penetrate the blood-brain barrier (BBB), during a state of BBB compromise such as with PRES, talc deposition may occur in the central nervous system.

Risk factors for wound-related complications after microvascular decompression.

Retrosigmoid craniotomy for microvascular decompression (MVD) has been traditionally performed via craniectomy. Various closure techniques have been described, yet factors associated with wound-related complications remain undetermined. Accordingly, herein, we sought to identify risk factors associated with wound-related complications after such procedures. An institutional retrospective case-control study was performed; outcomes of interest were cerebrospinal fluid (CSF) leak, wound dehiscence, wound infection, and pseudomeningocele. Univariate analysis was performed using Wilcoxon rank sum test for non-parametric continuous outcomes and chi-square test for categorical outcomes. Multivariate logistic regression was performed on binomial outcome variables. The study population included 197 patients who underwent MVD for trigeminal neuralgia (83.2%), hemifacial spasm (12.2%), vestibular nerve section (3.0%), and glossopharyngeal neuralgia (1.5%). The overall wound-related complication rate was 14.2% (n = 28), including twelve patients (6.1%) with CSF leak, ten patients (5.1%) with wound infection, ten patients (5.1%) with pseudomeningocele, and nine (4.6%) patients with wound dehiscence. Using multivariate logistic regression, preoperative anemia and current tobacco use were associated with significantly higher rates of complications (OR 6.01 and 4.58, respectively; p < 0.05), including CSF leak (OR 12.83 and 12.40, respectively, p < 0.05). Of note, use of synthetic bone substitute for cranioplasty was associated with a significantly lower rate of complications (OR 0.13, p < 0.01). Preoperative anemia and current tobacco use significantly increased, while synthetic bone substitute cranioplasty significantly decreased, odds of wound-related complications, the need for treatment, and CSF leaks. Additionally, higher BMI, longer operative duration, and prior radiosurgery may increase risk for wound-related complications.

Intraventricular metastatic melanoma: A case report and review of the literature.

Intraventricular melanoma is a very rare and highly malignant disease. Safe resection is the mainstay of treatment, but no standard guidelines exist for adjuvant therapy. Early histologic and molecular diagnosis is key for improved survival.

Incidence and risk factors for seizures associated with deep brain stimulation surgery.

OBJECTIVE: The objective of this study was to determine the incidence of seizures following deep brain stimulation (DBS) electrode implantation and to evaluate factors associated with postoperative seizures. METHODS: The authors performed a single-center retrospective case-control study. The outcome of interest was seizure associated with DBS implantation. Univariate analyses were performed using the Student t-test for parametric continuous outcomes. The authors used the Kruskal-Wallis test or Wilcoxon rank-sum test for nonparametric continuous outcomes, chi-square statistics for categorical outcomes, and multivariate logistic regression for binomial variables. RESULTS: A total of 814 DBS electrode implantations were performed in 645 patients (478 [58.7%] in men and 520 [63.9%] in patients with Parkinson's disease). In total, 22 (3.4%) patients who had undergone 23 (2.8%) placements experienced seizure. Of the 23 DBS implantation-related seizures, 21 were new-onset seizures (3.3% of 645 patients) and 2 were recurrence or worsening of a prior seizure disorder. Among the 23 cases with postimplantation-related seizure, epilepsy developed in 4 (17.4%) postoperatively; the risk of DBS-associated epilepsy was 0.50% per DBS electrode placement and 0.63% per patient. Nine (39.1%) implantation-related seizures had associated postoperative radiographic abnormalities. Multivariate analyses suggested that age at surgery conferred a modest increased risk for postoperative seizures (OR 1.06, 95% CI 1.02-1.10). Sex, primary diagnosis, electrode location and sidedness, and the number of trajectories were not significantly associated with seizures after DBS surgery. CONCLUSIONS: Seizures associated with DBS electrode placement are uncommon, typically occur early within the postoperative period, and seldom lead to epilepsy. This study suggests that patient characteristics, such as age, may play a greater role than perioperative variables in determining seizure risk. Multiinstitutional studies may help better define and mitigate the risk of seizures after DBS surgery.

Design and Rationale for First-in-Human Phase 1 Immunovirotherapy Clinical Trial of Oncolytic HSV G207 to Treat Malignant Pediatric Cerebellar Brain Tumors.

Brain tumors represent the most common pediatric solid neoplasms and leading cause of childhood cancer-related morbidity and mortality. Although most adult brain tumors are supratentorial and arise in the cerebrum, the majority of pediatric brain tumors are infratentorial and arise in the posterior fossa, specifically the cerebellum. Outcomes from malignant cerebellar tumors are unacceptable despite aggressive treatments (surgery, radiation, and/or chemotherapy) that are harmful to the developing brain. Novel treatments/approaches such as oncolytic virotherapy are urgently needed. Preclinical and prior clinical studies suggest that genetically engineered oncolytic herpes simplex virus (HSV-1) G207 can safely target cerebellar malignancies and has potential to induce an antitumor immune response at local and distant sites of disease, including spinal metastases and leptomeningeal disease. Herein, we outline the rationale, design, and significance of a first-in-human immunotherapy Phase 1 clinical trial targeting recurrent cerebellar malignancies with HSV G207 combined with a single low-dose of radiation (5 Gy), designed to enhance virus replication and innate and adaptive immune responses. We discuss the unique challenges of inoculating virus through intratumoral catheters into cerebellar tumors. The trial utilizes a single arm open-label traditional 3 + 3 design with four dose cohorts. The primary objective is to assess safety and tolerability of G207 with radiation in recurrent/progressive malignant pediatric cerebellar tumors. After biopsy to prove recurrence/progression, one to four intratumoral catheters will be placed followed by a controlled-rate infusion of G207 for 6 h followed by the removal of catheters at the bedside. Radiation will be given within 24 h of virus inoculation. Patients will be monitored closely for toxicity and virus shedding. Efficacy will be assessed by measuring radiographic response, performance score, progression-free and overall survival, and quality of life. The data obtained will be invaluable in our efforts to produce more effective and less toxic therapies for children with high-grade brain tumors.

Targeting glioma-initiating cells via the tyrosine metabolic pathway.

OBJECTIVE: Despite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism. METHODS: Comprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry. RESULTS: Metabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core. CONCLUSIONS: Selective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.

An Update on Neurofibromatosis Type 1-Associated Gliomas.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that affects children and adults. Individuals with NF1 are at high risk for central nervous system neoplasms including gliomas. The purpose of this review is to discuss the spectrum of intracranial gliomas arising in individuals with NF1 with a focus on recent preclinical and clinical data. In this review, possible mechanisms of gliomagenesis are discussed, including the contribution of different signaling pathways and tumor microenvironment. Furthermore, we discuss the recent notable advances in the developing therapeutic landscape for NF1-associated gliomas including clinical trials and collaborative efforts.

Tumor edge-to-core transition promotes malignancy in primary-to-recurrent glioblastoma progression in a PLAGL1/CD109-mediated mechanism.

BACKGROUND: Glioblastoma remains highly lethal due to its inevitable recurrence. Most of this recurrence is found locally, indicating that postsurgical tumor-initiating cells (TICs) accumulate at the tumor edge. These edge-TICs then generate local recurrence harboring new core lesions. Here, we investigated the clinical significance of the edge-to-core (E-to-C) signature generating glioblastoma recurrence and sought to identify its central mediators. METHODS: First, we examined the association of E-to-C-related expression changes to patient outcome in matched primary and recurrent samples (n = 37). Specifically, we tested whether the combined decrease of the edge-TIC marker PROM1 (CD133) with the increase of the core-TIC marker CD109, representing E-to-C transition during the primary-to-recurrence progression, indicates poorer patient outcome. We then investigated the specific molecular mediators that trigger tumor recurrence driven by the E-to-C progression. Subsequently, the functional and translational significance of the identified molecule was validated with our patient-derived edge-TIC models in vitro and in vivo. RESULTS: Patients exhibiting the CD133low/CD109high signature upon recurrence representing E-to-C transition displayed a strong association with poorer progression-free survival and overall survival among all tested patients. Differential gene expression identified that PLAGL1 was tightly correlated with the core TIC marker CD109 and was linked to shorter patient survival. Experimentally, forced PLAGL1 overexpression enhanced, while its knockdown reduced, glioblastoma edge-derived tumor growth in vivo and subsequent mouse survival, suggesting its essential role in the E-to-C-mediated glioblastoma progression. CONCLUSIONS: E-to-C axis represents an ongoing lethal process in primary glioblastoma contributing to its recurrence, partly in a PLAGL1/CD109-mediated mechanism.

Treatment of pediatric high-grade central nervous system tumors with high-dose methotrexate in combination with multiagent chemotherapy: A single-institution experience.

BACKGROUND: Effective treatment for pediatric embryonal brain tumors includes dose-intensive multiagent chemotherapy (DIMAC) followed by high-dose chemotherapy with stem cell rescue (HDCSCR). Use of repeated cycles of DIMAC including high-dose methotrexate (HDMTX) without HDCSCR has not been described. PROCEDURE: We retrospectively reviewed the responses/toxicities in 13 patients (aged 2-155 months, median 22 months) with central nervous system (CNS) tumors (atypical teratoid rhabdoid tumors, CNS embryonal tumors not otherwise specified, pineoblastoma, embryonal tumor with multilayered rosettes, and CNS sarcoma) treated over a 12-year period with repeated cycles of HDMTX followed by etoposide, cisplatin, cyclophosphamide, and vincristine. RESULTS: Six patients (46.2%) had disseminated disease at presentation and five (38.5%) had gross total resection. A total of 64 courses of therapy were administered with a median of five courses per patient.  Eight patients (61.5%) received radiation therapy (one at relapse). By completion of therapy, 11 patients (84.6%) achieved a response (six complete, five partial).  Six of the 13 patients (46.2%) remain alive with a median follow-up of 48 months (6-146).  Acute toxicities included fever/neutropenia (70.3%), bacteremia (15.6%), and grade 3 mucositis (18.8%).  Long-term complications included learning disability, seizure disorder, and brain necrosis, without treatment-related deaths. CONCLUSIONS: DIMAC with HDMTX without HDCSCR may be an effective treatment option for selected patients with embryonal or high-grade CNS tumors.

Cerebellar Arteriovenous Malformation Rupture Despite Apparent Angiographic Obliteration.

BACKGROUND: Arteriovenous malformations (AVMs) can occur in all regions of the brain and spinal cord, with clinical consequences and risks varying by location. Delayed AVM rupture despite digital subtraction angiography-confirmed obliteration post-radiation is exceedingly rare. CASE DESCRIPTION: To our knowledge, we present the first documented case of delayed hemorrhage associated with a cerebellar AVM 5 years after linear accelerator-based radiation in a man aged 31 years despite apparent angiographic obliteration. CONCLUSIONS: Intracranial hemorrhage after radiosurgery in digital subtraction angiography-confirmed obliterated AVMs is rare, with limited understanding of risk factors, appropriate preventative management, and mechanisms of occurrence. This case serves to demonstrate the need for greater awareness of this rare complication, as well as the need for appropriate surveillance and management strategies.

Artificial Intelligence in the Management of Glioma: Era of Personalized Medicine.

Purpose: Artificial intelligence (AI) has accelerated novel discoveries across multiple disciplines including medicine. Clinical medicine suffers from a lack of AI-based applications, potentially due to lack of awareness of AI methodology. Future collaboration between computer scientists and clinicians is critical to maximize the benefits of transformative technology in this field for patients. To illustrate, we describe AI-based advances in the diagnosis and management of gliomas, the most common primary central nervous system (CNS) malignancy. Methods: Presented is a succinct description of foundational concepts of AI approaches and their relevance to clinical medicine, geared toward clinicians without computer science backgrounds. We also review novel AI approaches in the diagnosis and management of glioma. Results: Novel AI approaches in gliomas have been developed to predict the grading and genomics from imaging, automate the diagnosis from histopathology, and provide insight into prognosis. Conclusion: Novel AI approaches offer acceptable performance in gliomas. Further investigation is necessary to improve the methodology and determine the full clinical utility of these novel approaches.

Patient Satisfaction in Spine Surgery: A Systematic Review of the Literature.

Patient satisfaction reflects the patients' perception of the outcome of care and is being considered for use in future reimbursement schemes. No consensus exists regarding the best instrument to measure patient satisfaction in the field of spine surgery. This systematic review aimed to determine how patient satisfaction for spine surgery has been measured previously and whether a disease-specific, comprehensive instrument to measure patient satisfaction has been established; we also aimed to define the dimensions of care that determine patient satisfaction in spine surgery. A systematic search of three online databases, unpublished sources, and citations was undertaken to identify 156 empirical studies that reported on patient satisfaction in the field of spine surgery. Manuscripts were reviewed in terms of the patient satisfaction instrument used, and the instruments were categorized as per content and method axes. Taxonomy of patient satisfaction with spine surgery identified the major characteristics of providers and medical care that influenced patient satisfaction and acted as a structure to categorically define the dimensions of patient satisfaction in spine surgery. The reviewed studies predominantly used global (108/156) rather than multidimensional (46/156), instruments. Most studies (96.2%) reported satisfaction with outcome rather than with care, and only 18.5% of the studies (29/156) utilized a disease-specific instrument. The following seven dimensions of patient status, outcome, and care experience that affected patient satisfaction were identified: pain, function, patient expectations/preference, specific patient health characteristics, caregiver interpersonal manner, efficacy/clinical outcomes, and postoperative care/therapy. Currently, no disease-specific instrument that includes all dimensions of patient satisfaction in spine surgery has been developed. Such a patient satisfaction instrument should be designed, tested for reliability and validity, and widely implemented.

Angiosarcoma of the Temporal Bone: Case Report and Review of the Literature.

BACKGROUND: Angiosarcomas are rare malignant tumors of endothelial origin. Nearly one half of all angiosarcomas occur in the head and neck. Temporal bone angiosarcomas are extremely uncommon. We present a case of temporal bone angiosarcoma and a review of the relevant data. CASE DESCRIPTION: We present the case of a 20-year-old man with a painful right postauricular mass after a closed head injury. Radiologic studies demonstrated a large right osteolytic and heterogeneously enhancing mass. The patient underwent right transpetrosal craniectomy for resection. Histologic studies confirmed high-grade sarcoma. Immunohistochemical staining demonstrated a uniformly positive ERG endothelial marker, CD31 staining with cytoplasmic and membranous patterns of immunopositivity, positive nuclear staining for FLI-1, positive cytoplasmic and membranous staining for CD99 and STAT6, and negative smooth muscle actin stains in the neoplastic cells. Ki-67 staining showed ∼94% positivity in the neoplastic cell nuclei. Postoperative follow-up imaging studies demonstrated evidence of metastatic right cervical lymphadenopathy. CONCLUSIONS: Angiosarcoma of the temporal bone is extremely uncommon. In the present case report, we explored a relationship between trauma and angiosarcoma of the temporal bone. We reviewed the reported data regarding the pathogenesis, diagnosis, treatment, radiologic findings, and histologic characteristics of angiosarcoma of the temporal bone.