SARS-CoV2 entry factors are expressed in primary human glioblastoma and recapitulated in cerebral organoid models.

PURPOSE: Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults with a median overall survival of only 14.6 months despite aggressive treatment. While immunotherapy has been successful in other cancers, its benefit has been proven elusive in GBM, mainly due to a markedly immunosuppressive tumor microenvironment. SARS-CoV-2 has been associated with the development of a pronounced central nervous system (CNS) inflammatory response when infecting different cells including astrocytes, endothelial cells, and microglia. While SARS-CoV2 entry factors have been described in different tissues, their presence and implication on GBM aggressiveness or microenvironment has not been studied on appropriate preclinical models. METHODS: We evaluated the presence of crucial SARS-CoV-2 entry factors: ACE2, TMPRSS2, and NRP1 in matched surgically-derived GBM tissue, cells lines, and organoids; as well as in human brain derived specimens using immunohistochemistry, confocal pixel line intensity quantification, and transcriptome analysis. RESULTS: We show that patient derived-GBM tissue and cell cultures express SARS-CoV2 entry factors, being NRP1 the most crucial facilitator of SARS-CoV-2 infection in GBM. Moreover, we demonstrate that, receptor expression remains present in our GBM organoids, making them an adequate model to study the effect of this virus in GBM for the potential development of viral therapies in the future. CONCLUSION: Our findings suggest that the SARS-CoV-2 virus entry factors are expressed in primary tissues and organoid models and could be potentially utilized to study the susceptibility of GBM to this virus to target or modulate the tumor microenviroment.

Interactive Neurosurgery Lecture Series: A Global Education Platform of Tele-Teaching During the Coronavirus Disease 2019 Pandemic and Beyond.

OBJECTIVE: To explore the worldwide impact of a virtual neurosurgery-neuroscience lecture series on optimizing neurosurgical education with tele-teaching. METHODS: A retrospective analysis was performed from our Zoom database to collect data from October 15, 2020, to December 14, 2020, and from September 27, 2021, to December 13, 2021. A comparative analysis of participants in the 2 different time frames was performed to investigate the impact of tele-teaching on neurosurgical education worldwide. To evaluate participant satisfaction, the yearly continuing medical education reports of 2020-2021 were analyzed. Data related to the distribution of lectures by subspecialties were also described. RESULTS: Among the 11 lectures of the first period, 257 participants from 17 countries in 4 different continents were recorded, with a mean of 64 (standard deviation = 9.30) participants for each meeting; 342 attendees participated from 19 countries in 5 continents over the 11 lectures of the second part, with an average of 82.8 (standard deviation = 14.04) attendees; a statistically significant increase in participation between the 2 periods was identified (P < 0.001) A total of 19 (2020) and 21 (2021) participants submitted the continuing medical education yearly survey. More than 86.4% of overall responses considered the lectures "excellent." The main topics reported during lectures in 2020-2021 were related to brain tumors (33.7%) and education (22.1%). CONCLUSIONS: The COVID-19 pandemic has increased the need to introduce new educational approaches for teaching novel ways to optimize patient care. Our multidisciplinary Web-based virtual lecture series could represent an innovative tele-teaching platform in neurosurgical training.

Utilizing Data from Wearable Technologies in the Era of Telemedicine to Assess Patient Function and Outcomes in Neurosurgery: Systematic Review and Time-Trend Analysis of the Literature.

BACKGROUND: The COVID-19 pandemic has driven the increased use of telemedicine and the adoption of wearable technology in neurosurgery. We reviewed studies exploring the use of wearables on neurosurgical patients and analyzed wearables' scientific production trends. METHODS: The review encompassed PubMed, EMBASE, Web of Science, and Cochrane Library. Bibliometric analysis was performed using citation data of the included studies through Elsevier's Scopus database. Linear regression was utilized to understand scientific production trends. All analyses were performed on R 4.1.2. RESULTS: We identified 979 studies. After screening, 49 studies were included. Most studies evaluated wearable technology use for patients with spinal pathology (n = 31). The studies were published over a 24-year period (1998-2021). Forty-seven studies involved wearable device use relevant to telemedicine. Bibliometric analysis revealed a compounded annual growth rate of 7.3%, adjusted for inflation, in annual scientific production from 1998 to 2021 (coefficient=1.3; 95% Confidence Interval = [0.7, 1.9], P < 0.01). Scientific production steadily increased in 2014 (n = 1) and peaked from 2019 (n = 8) to 2021 (n = 13) in correlation with the COVID-19 pandemic. Publications spanned 34 journals, averaged 24.4 citations per article, 3.0 citations per year per article, and 8.3 authors per article. CONCLUSION: Wearables can provide clinicians with objective measurements to determine patient function and quality of life. The rise in articles related to wearables in neurosurgery demonstrates the increased adoption of wearable devices during the COVID-19 pandemic. Wearable devices appear to be a key component in this era of telemedicine and their positive utility and practicality are increasingly being realized in neurosurgery.

Creation of a Proof-of-Concept 3D-Printed Spinal Lateral Access Simulator.

Background Minimally invasive lateral lumbar interbody fusion (LLIF) offers advantages over traditional approaches, providing indirect decompression of neural elements and deformity correction while avoiding many challenges and risks of anterior and posterior approaches. Mastering this technique requires a specialized team, advanced equipment, and sufficient case exposure. Current training is limited to the classic educational model, and alternative training methods such as cadaver labs can be inconvenient, inaccessible, expensive, and incompatible with intraoperative neuromonitoring (IONM) systems. Objective The aim of this study was to create a proof-of-concept, low-cost, fully synthetic lateral lumbar surgical simulator and to increase awareness of the lack of current training alternatives. Methods Standard engineering design and expert interviews of attending neurosurgeons, nurses, engineers, and medical device representatives (n=20) were utilized to determine key elements for the simulator, physical characteristics of the components, and translational strategy. Physical and radiographic testing was performed on multiple thermoplastics to determine appropriateness for inclusion in the simulator. For evaluation of the concept, a descriptive slide deck and questionnaire were sent to 15 U.S. and 15 international surgeons who perform LLIF. Results The lateral access training model (LATM) features the following three components: torso casing, spine module, and IONM feature. This model utilizes operable ABS (acrylonitrile butadiene styrene) 3D-printed lumbar vertebrae, verified for anatomical accuracy and compatibility with fluoroscopy. Additionally, a novel neuromonitoring simulation algorithm was developed to train junior residents on neurological complications. To further highlight the need for lateral training models, 30/30 polled surgeons felt that this simulator has value for the field, 29/30 noted that they would have used the LATM if they had access during training, and 30/30 responded that they would encourage trainees to practice on the LATM. Conclusion The LATM is a first step to provide reliable and inexpensive basic lateral lumbar spine training. While this model is lacking some anatomical features, our simulator offers novel training elements for lateral lumbar transpsoas approaches, which lay the foundation for future models to be built. The need for this training exists, and current gaps in the approach to learning these complex techniques need to be filled due to the inconvenience, cost, and impracticability of standard cadaveric models.

Directed stimulation of the dentato-rubro-thalamic tract for deep brain stimulation in essential tremor: a blinded clinical trial.

OBJECTIVE: Observational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming. METHODS: A prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn-Tolosa-Marín tremor rating score compared to the preoperative baseline. RESULTS: Among the six patients, tremor rating scores differed significantly among the three experimental conditions (P=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; P=0.031) and standard-of-care programming (50.7% ± 19.2%; P=0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R2=0.24; P=0.04). No significant adverse events were encountered. CONCLUSIONS: Using a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.

Impact of COVID-19 on Neurosurgery in Brazil's Health System: The Reality of a Developing Country Affected by the Pandemic.

BACKGROUND: The coronavirus disease identified in 2019 (COVID-19) pandemic changed neurosurgery protocols to provide ongoing care for patients while ensuring the safety of health care workers. In Brazil, the rapid spread of the disease led to new challenges in the health system. Neurooncology practice was one of the most affected by the pandemic due to restricted elective procedures and new triage protocols. We aim to characterize the impact of the pandemic on neurosurgery in Brazil. METHODS: We analyzed 112 different types of neurosurgical procedures, with special detail in 11 neurooncology procedures, listed in the Brazilian Hospital Information System records in the DATASUS database between February and July 2019 and the same period in 2020. Linear regression and paired t-test analyses were performed and considered statistically significant at P < 0.05. RESULTS: There was an overall decrease of 21.5% (28,858 cases) in all neurosurgical procedures, impacting patients needing elective procedures (-42.46%) more than emergency surgery (-5.93%). Neurooncology procedures decreased by 14.89%. Nonetheless, the mortality rate during hospitalization increased by 21.26%. Linear regression analysis in hospitalizations (Slope = 0.9912 ± 0.07431; CI [95%] = 0.8231-1.159) and total cost (Slope = 1.03 ± 0.03501; CI [95%] = 0.9511-1.109) in the 11 different types of neurooncology procedures showed a P < 0.0001. The mean cost per type of procedure showed an 11.59% increase (P = 0.0172) between 2019 and 2020. CONCLUSIONS: The COVID-19 pandemic has increased mortality, decreased hospitalizations, and therefore decreased overall costs, despite increased costs per procedure for a variety of neurosurgical procedures. Our study serves as a stark example of the effect of the pandemic on neurosurgical care in settings of limited resources and access to care.

Outcomes and Surgical Considerations for Neurosurgical Patients Hospitalized with COVID-19-A Multicenter Case Series.

OBJECTIVE: Neurosurgical patients are at a higher risk of having a severe course of coronavirus disease 2019 (COVID-19). The objective of this study was to determine morbidity, hospital course, and mortality of neurosurgical patients during the coronavirus disease 2019 (COVID-19) pandemic in a multicenter health care system. METHODS: A retrospective observational study was conducted to identify all hospitalized neurosurgical patients positive for COVID-19 from March 11, 2020 to November 2, 2020 at Mayo Clinic and the Mayo Clinic Health System. RESULTS: Eleven hospitalized neurosurgical patients (0.68%) were positive for COVID-19. Four patients (36.6%) were men and 7 (63.3%) were women. The mean age was 65.7 years (range, 35-81 years). All patients had comorbidities. The mean length of stay was 13.4 days (range, 4-30 days). Seven patients had a central nervous system malignancy (4 metastases, 1 meningioma, 1 glioblastoma, and 1 schwannoma). Three patients presented with cerebrovascular complications, comprising 2 spontaneous intraparenchymal hemorrhages and 1 ischemic large-vessel stroke. One patient presented with an unstable traumatic spinal burst fracture. Four patients underwent neurosurgical/neuroendovascular interventions. Discharge disposition was to home in 5 patients, rehabilitation facility in 3, and hospice in 3. Five patients had died at follow-up, 3 within 30 days from COVID-19 complications and 2 from progression of their metastatic cancer. CONCLUSIONS: COVID-19 is rare among the inpatient neurosurgical population. In all cases, patients had multiple comorbidities. All symptomatic patients from the respiratory standpoint had complications during their hospitalization. Deaths of 3 patients who died within 30 days of hospitalization were all related to COVID-19 complications. Neurosurgical procedures were performed only if deemed emergent.

Retrosigmoid Craniectomy and Suprameatal Drilling-3-Dimensionally Printed Microneurosurgical Simulation: 2-Dimensional Operative Video.

Neurosurgical training is being challenged by rigorous work-hour restrictions and the COVID-19 pandemic.1 Now, more than ever, surgical simulation plays a pivotal role in resident education and psychomotor skill development. Three-dimensional (3D) printing technologies enable the construction of inexpensive, patient-specific, anatomically accurate physical models for a more convenient and realistic simulation of complex skull base approaches in a safe environment.2 All stages of the surgical procedure can be simulated, from positioning and exposure to deep microdissection, which has an unparalleled educational value. The complex approach-specific anatomy, narrow working angles, and pathoanatomic relationships can be readily explored from the surgeon's perspective or point of view.2,3 Furthermore, different thermoplastic polymers can be utilized to replicate the visual and tactile feedback of bone (cortical/cancellous), neurological, and vascular tissues.4 Retrosigmoid craniectomies are widely used in neurosurgery with various applications, including microvascular decompressions in patients with trigeminal neuralgia.5-7 Removal of the suprameatal tubercle (SMT) extends the retrosigmoid approach superiorly to the middle fossa and Meckel's cave, and anteriorly to the clivus.8,9 This maneuver may be necessary in patients with prominent SMTs obstructing the view of the trigeminal nerve and in patients with a more anterosuperior neurovascular conflict. This video illustrates a microsurgical training tool for learning and honing the technique of retrosigmoid craniectomy and suprameatal drilling using an affordable (29.00 USD) biomimetic 3D-printed simulator that closely recapitulates not only the anatomy but also the tactile feedback of drilling and manipulating neurological tissues (see Table and Graph 1; minute 07:11) as it happens at the time of surgery.

Path to Reopening Surgery during the COVID-19 Pandemic: Neurosurgery Experience

INTRODUCTION The COVID-19 pandemic created a major public health threat to patients and health care systems around the world. Many hospitals cancelled elective surgeries to brace for the pandemic thus impacting many neurosurgical patients that had their surgeries postponed. METHODS We implemented several measures for staff and patients to minimize the risk of exposure to SARS-CoV-2. For surgical clearance, all patients needed to be tested for SARS-CoV-2 within 48h prior to the non-elective surgery. A triage protocol was implemented to manage patients in need of non-elective surgeries. A “drive-through” testing center was developed for preoperative surgical clearance to triage cases in need of non-elective surgery. Similarly, all patients admitted to the hospital were tested. Telemedicine played a big role in evaluating the need of surgery. We reviewed the clinical, radiographic, and laboratory data for all patients that underwent surgery within the neurosurgery department from March 26th to April 22nd 2020. RESULTS Using a combination of preoperative outpatient COVID-19 drive-through and inpatient testing to help obtain surgical clearance with selected telemedicine evaluations, 103 non-elective neurosurgical procedures were performed on 102 patients. No patients tested positive for the COVID-19 testing prior to surgery. None of the operated patients developed any COVID-19 symptoms during their hospitalization or were re-admitted to our ED postoperatively for COVID-19 symptoms. A subset of patients developed symptoms suspect for COVID-19 post-operatively but were retested and all tested negative. CONCLUSION We describe a multi-faceted preoperative triage protocol for safely performing non-elective neurosurgical cases during the COVID-19 pandemic, which could help other neurosurgical departments and hospitals minimize coronavirus exposure for patients and healthcare workers. We believe this triage strategy helps safely identify selected patients in need of neurosurgical care amidst hospital capacity concerns, COVID-19 testing limitations, limited personal protective equipment, and this approach could be implemented at other centers to gradually restart a process towards elective surgeries in a safe way.

Telemedicine in Neurosurgery During the COVID-19 Pandemic and Beyond

INTRODUCTION The COVID-19 pandemic has significantly impacted patients and health care systems around the globe. Hospitals cancelled elective surgeries and telemedicine was adopted as a common tool to keep providing care while minimizing patients' risk of exposure to SARS-CoV-2. METHODS To respond to the spread of SARS-CoV-2 we implemented several measures to contribute to flattening the COVID-19 curve. Our neurosurgery department performed an evaluation of the upcoming clinic visits, and either converted to telemedicine or rescheduled patients that were considered not to be significantly impacted by a postponement. Until March 2020 almost 100% of our clinic visits were face-to-face, in April 55% of our clinic visits were via telemedicine. Telemedicine was performed as video with audio or by telephone call. Video visits were conducted via the application Zoom due to its HIPPA compliance and its integration with the electronic medical record Epic. RESULTS Telemedicine played a key role in our strategy to prioritize in person care for neurosurgical patients in need of urgent care while maintaining follow-ups and avoiding delays in care for other patients. During the month of April our neurosurgery department performed 315 telemedicine visits among all the different subspecialties. 172 (55%) were phone consults, 143 (45%) video consults;101 (32%) were new consults, 195 (62%) return visits, 18 (6) post-operative follow-ups. New consults were mainly carried-out as video with audio, while return visits and post-operative follow-ups were predominantly phone calls. Only 39 (12%) of this patients required surgery. CONCLUSION We describe our experience with telemedicine in neurosurgery as an effective tool to provide care during the COVID-19 pandemic while decreasing the risk of transmission of the virus. There are still many regulatory requirements to be addressed, but telemedicine emerged from this pandemic as a valuable tool to conduct neurosurgical visits that in the future can potentially relieve the burden of travel seeking medical opinions at tertiary centers.

Nervous system involvement in SARS-coronavirus infection: a review on lessons learned from the previous outbreaks, ongoing pandemic and what to expect in the future.

Viral infections have been associated with the deleterious damage to nervous system resulting in impairment of the central nervous system as late sequalae infections. Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), several studies have reported patients developing adverse neurological signs and symptoms. Like the outbreak of SARS in 2003, the recent outbreak has undermined the norm of the nervous system. This review will summarize the possible mechanism of neurological manifestations, the clinical presentations of patients with such symptoms secondary to SARS coronaviruses, and the prospective role of neurology and neurosurgery practice in managing these symptoms in the current climate.

Telemedicine Utilization in Neurosurgery During the COVID-19 Pandemic: A Glimpse Into the Future?

OBJECTIVE: To describe telemedicine utilization in neurosurgery at a single tertiary institution to provide outpatient care during the coronavirus disease 2019 (COVID-19) pandemic, with 315 telemedicine visits performed by the neurosurgery department. PATIENTS AND METHODS: In response to the COVID-19 pandemic national stay-at-home orders and postponed elective surgeries, we converted upcoming clinic visits into telemedicine visits and rescheduled other patients thought not to be markedly affected by surgical postponement. We reviewed the charts of all patients who had telehealth visits from April 1 through April 30, 2020, and collected demographic information, diagnosis, type of visit, and whether they received surgery; a satisfaction questionnaire was also administered. RESULTS: In March 2020, 94% (644 of 685) of the neurosurgery clinic visits were face-to-face, whereas in April 2020, 55% (315 of 573) of the visits were telemedicine (P<.001). In April, of the 315 telemedicine visits, 172 (55%) were phone consults and 143 (45%) video consults; 101 (32%) were new consults, 195 (62%) return visits, and 18 (6%) postoperative follow-up. New consults were more likely to be video with audio than return visits and postoperative follow-up (P<.001). Only 39 patients (12%) required surgery. Ninety-one percent of the questionnaire respondents were very likely to recommend telemedicine. CONCLUSION: Rapid implementation of telemedicine to evaluate neurosurgery patients became an effective tool for preoperative consultation, postoperative and follow-up visits during the COVID-19 pandemic, and decreased risks of exposure to severe acute respiratory syndrome coronavirus 2 to patients and health care staff. Future larger studies should investigate the cost-effectiveness of telemedicine used to triage surgical from nonsurgical patients, potential cost-savings from reducing travel burdens and lost work time, improved access, reduced wait times, and impact on patient satisfaction.

Path to Reopening Surgery in the COVID-19 Pandemic: Neurosurgery Experience.

OBJECTIVE: To test the efficacy of an innovative coronavirus disease 2019 (COVID-19) preoperative triage protocol as a way to gradually reopen and ramp-up elective surgeries. PATIENTS AND METHODS: We reviewed clinical, radiographic, and laboratory data for all patients who underwent surgery within the neurosurgery department from March 26 through April 22, 2020. We collected data on demographic information, comorbidities, preoperative COVID-19 test results, whether COVID-19 respiratory or other symptoms were developed during hospitalization, hospital length of stay, discharge disposition, and postoperative COVID-19 test results. RESULTS: Using a combination of both preoperative outpatient COVID-19 drive-through and inpatient testing to obtain surgical clearance with selected telemedicine evaluations, 103 nonelective neurosurgical procedures were performed in 102 patients. No patients tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 48 hours before surgery. None of the patients developed any COVID-19 symptoms during their hospitalization or were readmitted to our emergency department postoperatively for COVID-19 symptoms. CONCLUSION: We describe a multifaceted preoperative triage protocol for safely performing nonelective neurosurgical procedures during the COVID-19 pandemic, which could help other neurosurgical departments and hospitals minimize coronavirus exposure for patients and health care workers. We believe this triage strategy could be implemented at other centers to gradually restart a process toward elective surgeries in a safe way.