Successful adaptation of twinning concept for global neurosurgery collaborations-a validation study.

INTRODUCTION: Globally, many regions have an urgent, unmet need of neurosurgical care. A multi-step neurosurgical twinning technique, International Neurosurgical Twinning Modeled for Africa (INTIMA), was proved to be successful during a previous mission to Neurosurgical Unit, Enugu, Nigeria. The Swedish African Neurosurgical Collaboration (SANC) performed a developmental mission together with the local neurosurgical unit in The Gambia, adopting the INTIMA model. METHODS: A multidisciplinary team visited for a 2-week collaborative mission at the Neurosurgical Department of the Edward Francis Small Teaching Hospital in Banjul, The Gambia. The mission followed the data of neurosurgical operations during and after the mission as well as about the operations 3 months prior to and after the mission was collected. RESULTS: During the mission, a total of 22 operations was carried out, the most common being degenerative spinal conditions (n = 9). In the 3 months following the mission, 43 operations were performed compared to 24 during the 3 months leading up to the mission. The complexity of the performed procedures increased after the mission. An operating microscope (Möller-Wedel) was donated and installed and the neurosurgeons on site underwent training in microneurosurgery. The surgical nurses, nurses at the postoperative ward, and the physiotherapists underwent training. A biomedical engineer serviced multiple appliances and devices improving the patient care on site while training local technicians. CONCLUSION: This study validated the use of the INTIMA model previously described in a mission by Swedish African Neurosurgical Collaboration (SANC). The model is sustainable and produces notable results. The core strength of the model is in the multidisciplinary team securing all the aspects and steps of the neurosurgical care. Installation of an operating microscope opened for further microsurgical possibilities, improving the neurosurgical care in The Gambia.

Is a drainage time of less than 24 h sufficient after chronic subdural hematoma evacuation?

BACKGROUND: It is well established that the use of a postoperative drain after chronic subdural hematoma surgery reduces recurrence rates, and it is common to use a postoperative drain for longer than 24 h. It is unclear whether this is superior to a shorter drainage time of less than 24 h. Our aim was to compare a postoperative drainage longer or shorter than 24 h after chronic subdural hematoma evacuation. MATERIALS AND METHODS: In this retrospective single centre study, 207 adult patients undergoing chronic subdural hematoma evacuation with a postoperative drainage longer (LDT-group) or shorter (SDT-group) than 24 h were compared regarding recurrence, mortality within 6 months and complications requiring hospital admission within 30 days. Length of hospital stay was also recorded. An active subgaleal drain was used. In addition to the retrospective cohort, we also studied the total volume drained per hour after cSDH surgery in a prospective cohort of 10 patients. RESULTS: Recurrence occurred in 12/96 (12.5%) in the LDT-group and in 13/111 (11.7%) patients in the SDT-group (p = 0.15). There was no significant difference between groups regarding recurrence, complications or mortality. The prospective cohort showed that most of the drainage occurred within the first hours after surgery. CONCLUSION: Our data show that a postoperative drainage duration of less than 24 h does not lead to an increase in recurrence, complications or mortality compared to a drainage time of more than 24 h. A shorter drainage duration (< 24 h) after cSDH surgery facilitated earlier mobilisation and shorter hospital stay.

Effect of Irrigation Fluid Temperature on Recurrence in the Evacuation of Chronic Subdural Hematoma: A Randomized Clinical Trial.

Importance: The effect of a physical property of irrigation fluid (at body vs room temperature) on recurrence rate in the evacuation of chronic subdural hematoma (cSDH) needs further study. Objective: To explore whether irrigation fluid temperature has an influence on cSDH recurrence. Design, Setting, and Participants: This was a multicenter randomized clinical trial performed between March 16, 2016, and May 30, 2020. The follow-up period was 6 months. The study was conducted at 3 neurosurgical departments in Sweden. All patients older than 18 years undergoing cSDH evacuation during the study period were screened for eligibility in the study. Interventions: The study participants were randomly assigned by 1:1 block randomization to the cSDH evacuation procedure with irrigation fluid at room temperature (RT group) or at body temperature (BT group). Main Outcomes and Measures: The primary end point was recurrence requiring reoperation within 6 months. Secondary end points were mortality, health-related quality of life, and complication frequency. Results: At 6 months after surgery, 541 patients (mean [SD] age, 75.8 [9.8] years; 395 men [73%]) had a complete follow-up according to protocol. There were 39 of 277 recurrences (14%) requiring reoperation in the RT group, compared with 16 of 264 recurrences (6%) in the BT group (odds ratio, 2.56; 95% CI, 1.38-4.66; P < .001). There were no significant differences in mortality, health-related quality of life, or complication frequency. Conclusions and Relevance: In this study, irrigation at body temperature was superior to irrigation at room temperature in terms of fewer recurrences. This is a simple, safe, and readily available technique to optimize outcome in patients with cSDH. When irrigation is used in cSDH surgery, irrigation fluid at body temperature should be considered standard of care. Trial Registration: ClincalTrials.gov Identifier: NCT02757235.

Endoscopic versus open microsurgery for colloid cysts of the third ventricle.

PURPOSE: The surgical approach for colloid cysts of the third ventricle mainly consists of endoscopic or microscopic approach but few studies compare the neurologic outcomes and complications related to the different approaches. We retrospectively reviewed our results after resection of colloid cysts of the third ventricle using endoscopic surgery (ES) compared to open microsurgery (OS). METHODS: Fifty-one patients were included in the study of which 17 patients underwent ES. Colloid cyst size and Evans' index were evaluated on CT or MRI scans. Presenting symptoms, neurologic outcomes and complications were compared between the two groups and analysed using Fisher's exact test. Operative time and days of hospital stay were compared between the two groups, using independent sample t-test. The median follow-up time was 96 days and did not differ significantly between the groups. RESULTS: Shorter mean operative time (p = 0.04) and fewer days of hospital stay (p < 0.01) were found in the endoscopic group compared to the open microsurgical group. Presenting symptoms, neurological outcomes and postoperative complications were similar in the two groups. CONCLUSIONS: ES showed similar neurologic outcomes and complications compared to OS for colloid cysts of the third ventricle. ES showed significantly shorter operative times and hospital stays compared to OS.

Global neurosurgery over a 60-year period: Conceptual foundations, time reference, emerging Co-ordinates and prospects for collaborative interventions in low and middle income countries.

Introduction: We evaluated salient initiatives invested in global neurosurgery over a 60-year period. Research question: What are the Phases, Achievements, Challenges, and Lessons of Global Neurosurgery. Methods: A 60-year retrospective study from 1960 to 2020 analyzing the major phases, lessons, and progress notes. We reviewed the foundational need questions and innovated tools used to answer them. Results: Three phases defining our study period were identified. In the early phase, birthing academic units and the onset of individual volunteerism were dominant concepts. The 2nd phase is summarized by the rise of volunteerism and surgical camps.The third phase is heralded by advocacy and strategies for achieving care equity. The defining moment is the Lancet commission for global surgery summit in 2015. Lessons include the need for evaluation of the resources of recipient and donor locations using novel global surgery tools. Conclusion: Global neurosurgery over the 60-year study period is summarized by indelible touchstones of personal and group efforts as well as triumphs derived from innovations in the face of formidable challenges.

Working in low- and middle-income countries: Learning from each other.

•Barriers may limit LMICs-HICs collaborations: infrastructure, equipment's lack/inadequacy, political issues, brain drain.•Local training is crucial for universal health coverage; several activities are headed by Global Neurosurgery organisations.•The â€‹EANS Global and Humanitarian Neurosurgery Committee aims to become a gateway for partnerships between HICs and LMICs.

Novel TPR::ROS1 Fusion Gene Activates MAPK, PI3K and JAK/STAT Signaling in an Infant-type Pediatric Glioma.

BACKGROUND/AIM: Although fusion genes involving the proto-oncogene receptor tyrosine kinase ROS1 are rare in pediatric glioma, targeted therapies with small inhibitors are increasingly being approved for histology-agnostic fusion-positive solid tumors. PATIENT AND METHODS: Here, we present a 16-month-old boy, with a brain tumor in the third ventricle. The patient underwent complete resection but relapsed two years after diagnosis and underwent a second operation. The tumor was initially classified as a low-grade glioma (WHO grade 2); however, methylation profiling suggested the newly WHO-recognized type: infant-type hemispheric glioma. To further refine the molecular background, and search for druggable targets, whole genome (WGS) and whole transcriptome (RNA-Seq) sequencing was performed. RESULTS: Concomitant WGS and RNA-Seq analysis revealed several segmental gains and losses resulting in complex structural rearrangements and fusion genes. Among the top-candidates was a novel TPR::ROS1 fusion, for which only the 3' end of ROS1 was expressed in tumor tissue, indicating that wild type ROS1 is not normally expressed in the tissue of origin. Functional analysis by Western blot on protein lysates from transiently transfected HEK293 cells showed the TPR::ROS1 fusion gene to activate the MAPK-, PI3K- and JAK/STAT- pathways through increased phosphorylation of ERK, AKT, STAT and S6. The downstream pathway activation was also confirmed by immunohistochemistry on tumor tissue slides from the patient. CONCLUSION: We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse.

Surgical outcomes of pediatric brain tumors in Sub-Saharan Africa: A systematic review.

Background: Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income countries (LMIC) remains low despite advances in neurosurgical care and diagnostics over the past decades. The aim of this systematic review was to investigate the surgical outcomes for PBT in Sub-Saharan Africa, and the distribution of PBT types. Methods: A systematic review was conducted on PubMed, for all available literature on the surgical outcomes of PBT in Sub-Saharan Africa, published before May 3, 2022. Two reviewers performed abstract, full text screening and data collection independently, resolving any conflicts by consensus. Results: The search yielded 256 studies, of which 22 met the inclusion criteria, amounting to a total of 243 patients. Nigeria was the country with most data. Only subgroups of patients could be extracted from 12 studies, and variables of interest in 6 studies had inconsistent sample sizes. The age centered around 9 years, and there were approximately equal number of girls and boys. The most common tumor was medulloblastoma, followed by craniopharyngioma and astrocytoma. There was large heterogeneity in the reporting of outcomes, and a trend was difficult to discern, considering the large number of different tumor types and different extents of resection. Discussion and conclusion: Data is insufficient and inconsistent, precluding statistical conclusions. There is a need for more studies in the field.

Global neurosurgery amongst the EANS community: Where are we at?

•Awareness of Global Neurosurgery opportunities is limited in the EANS and a minority have had previous experiences with such activities.•Most training programs and job environments don't encourage participation in Global Neurosurgery and mentors are lacking.•However, most European neurosurgeons and trainees remain interested in Global Neurosurgery and are willing to participate.•Junior trainees is the group with the highest rate of interest for Global Neurosurgery.•Barriers exist that may limit participation in Global Neurosurgery, and funding is the most relevant.

DNA methylation alterations across time and space in paediatric brain tumours.

DNA methylation is increasingly used for tumour classification and has expanded upon the > 100 currently known brain tumour entities. A correct diagnosis is the basis for suitable treatment for patients with brain tumours, which is the leading cause of cancer-related death in children. DNA methylation profiling is required for diagnosis of certain tumours, and used clinically for paediatric brain tumours in several countries. We therefore evaluated if the methylation-based classification is robust in different locations of the same tumour, and determined how the methylation pattern changed over time to relapse. We sampled 3-7 spatially separated biopsies per patient, and collected samples from paired primary and relapse brain tumours from children. Altogether, 121 samples from 46 paediatric patients with brain tumours were profiled with EPIC methylation arrays. The methylation-based classification was mainly homogeneous for all included tumour types that were successfully classified, which is promising for clinical diagnostics. There were indications of multiple subclasses within tumours and switches in the relapse setting, but not confirmed as the classification scores were below the threshold. Site-specific methylation alterations did occur within the tumours and varied significantly between tumour types for the temporal samples, and as a trend in spatial samples. More alterations were present in high-grade tumours compared to low-grade, and significantly more alterations with longer relapse times. The alterations in the spatial and temporal samples were significantly depleted in CpG islands, exons and transcription start sites, while enriched in OpenSea and regions not affiliated with a gene, suggesting a random location of the alterations in less conserved regions. In conclusion, more DNA methylation changes accumulated over time and more alterations occurred in high-grade tumours. The alterations mainly occurred in regions without gene affiliation, and did not affect the methylation-based classification, which largely remained homogeneous in paediatric brain tumours.

Pilot application of Lecture-Panel-Discussion Model (LPDM) in global collaborative neurosurgical education: a novel training paradigm innovated by the Swedish African Neurosurgery Collaboration.

BACKGROUND: Disruptions in global surgery educational routines by the COVID-19 pandemic have elicited demands for alternative formats for rendering qualitative neurosurgical education. This study presents application of a novel model of online neurosurgical course, the Lecture-Panel-Discussion Model (LPDM). METHODS: This is a cross-sectional survey of participants who attended the Swedish African Neurosurgery Collaboration (SANC)-100A course. Participants evaluated the course through an online self-administered questionnaire using a 5-point Likert scale ranging from very poor-1, poor-2, average (fair)-3, good-4, to excellent-5. SANC-100A comprises a tripod of Lectures, Panel review, and interactive case Discussion. This model (LPDM) was innovated by SANC and applied at the Enugu International Neurosurgery course in February 2021. RESULTS: There were 71 attendees, 19 were course faculty, while 52 were participants. Thirty-five attended from Nigeria, 11 from Sweden, 3 from Malawi, 2 from Senegal, and 1 from the UK. Among 44 participants who completed the questionnaire, there were 9 fellows and 35 residents. The overall median course Likert rating was 4.65 ± 0.1. The median overall rating for course events was similar between day 1 (Likert score = 4.45) and day 2 (Likert score = 4.55), U = 55, Z score = 1.10, P = 0.27. The median rating for lectures was 4.50 ± 0.2 and varied from 4.40 on day 1 to 4.55 on day 2. The median rating for panel review was 4.60 ± 0.1 and varied from 4.55 on day 1 to 4.65 on day 2. Interactive case discussions were rated 4.80 on both course days. There was a significant variability in the rating profiles of the course tripod: U = 24.5, P = 0.03. Fifty-one (98%) participants believe LPDM was COVID-19-compliant, while 90% believe the course was beneficial to training and practice. CONCLUSION: Initial application of LPDM is rewarded with both high acceptance and high rating among participants.

Discovery of a rare GKAP1-NTRK2 fusion in a pediatric low-grade glioma, leading to targeted treatment with TRK-inhibitor larotrectinib.

Here we report a case of an 11-year-old girl with an inoperable tumor in the optic chiasm/hypothalamus, who experienced several tumor progressions despite three lines of chemotherapy treatment. Routine clinical examination classified the tumor as a BRAF-negative pilocytic astrocytoma. Copy-number variation profiling of fresh frozen tumor material identified two duplications in 9q21.32-33 leading to breakpoints within the GKAP1 and NTRK2 genes. RT-PCR Sanger sequencing revealed a GKAP1-NTRK2 exon 10-16 in-frame fusion, generating a putative fusion protein of 658 amino acids with a retained tyrosine kinase (TK) domain. Functional analysis by transient transfection of HEK293 cells showed the GKAP1-NTRK2 fusion protein to be activated through phosphorylation of the TK domain (Tyr705). Subsequently, downstream mediators of the MAPK- and PI3K-signaling pathways were upregulated in GKAP1-NTRK2 cells compared to NTRK2 wild-type; phosphorylated (p)ERK (3.6-fold), pAKT (1.8- fold), and pS6 ribosomal protein (1.4-fold). Following these findings, the patient was enrolled in a clinical trial and treated with the specific TRK-inhibitor larotrectinib, resulting in the arrest of tumor growth. The patient's condition is currently stable and the quality of life has improved significantly. Our findings highlight the value of comprehensive clinical molecular screening of BRAF-negative pediatric low-grade gliomas, to reveal rare fusions serving as targets for precision therapy.

Should neurosurgeons continue to work in the absence of personal protective equipment during the COVID-19 era?

The COVID-19 pandemic has resulted in a widespread shortage of personal protective equipment (PPE). Many healthcare workers, including neurosurgeons, have expressed concern about how to safely and adequately perform their medical responsibilities in these challenging circumstances. One of these concerns revolves around the pressing question: should providers continue to work in the absence of adequate PPE? Although the first peak of the COVID-19 crisis seems to have subsided and supply of PPE has increased, concerns about insufficient PPE availability remain. Inconsistent supply, limited efficacy, and continued high demand for PPE, combined with the continued threat of a second COVID-19 wave, mean that the issues surrounding PPE availability remain unresolved, including a duty to work. This paper offers an ethical investigation of whether neurosurgeons should perform their professional responsibilities with limited availability of PPE. We evaluate ethical considerations and conflicting duties and thereby hope to facilitate providers in making a well-considered personal and moral decision about this challenging issue.

Pediatric brain tumor care in a Sub-Saharan setting: current poise of a precariously loaded dice.

OBJECTIVE: To evaluate the current status of pediatric brain tumor (PBT) care and identify determinants and profiles of survival and school attendance. METHODS: An 8-year institution-based prospective longitudinal study. All cases investigated with neuroimaging and treated were enrolled. Data was analyzed with SPSS (Inc) Chicago IL, USA version 23. Chi Square test, One-way ANOVA and confidence limits were used to evaluate associations at the 95% level of significance. Ethical approval for our study was obtained Health Research Ethics Committee of our hospital. RESULTS: Among 103 patients enrolled, 92 satisfied our study criteria. There were 45 males and 39 females, M: F = 0.8. The mean age was 9.5 ± 2.1 years 95%CI with a range of 7 months to 16 years. The most common symptom was headache for supratentorial lesions (73%) and gait disturbance (80.2%) for infratentorial lesions. More tumors were supratentorial in location 51 (55.4%), 35 (38.1%) were infratentorial and 6 (6.5%) were transtentorial. Craniopharyngiomas (n = 23), medulloblastomas (n = 22) and astrocytomas (n = 15) were the most common tumors. Hemoglobin genotype (AA and AS) had some influence on tumor phenotype FT, P = 0.033. 76 cases were microsurgically resected while 16 patients were treated with radiotherapy alone. The 30-day mortality for operated cases is 7.2 ± 0.7%. Overall 1-year and 5-year survival was 66.7 and 52.3%, respectively. School attendance, performance and outcome varied among treatment subgroups. CONCLUSION: Survival profile in this series suggests some improvement in comparison to previous studies from our region, Hemoglobin genotype profiles may signature paediatric brain tumor phenotypes in our setting.

Ethical triage during the COVID-19 pandemic: a toolkit for neurosurgical resource allocation.

BACKGROUND: The COVID-19 pandemic confronts healthcare workers, including neurosurgeons, with difficult choices regarding which patients to treat. METHODS: In order to assist ethical triage, this article gives an overview of the main considerations and ethical principles relevant when allocating resources in times of scarcity. RESULTS: We discuss a framework employing four principles: prioritizing the worst off, maximizing benefits, treating patients equally, and promoting instrumental value. We furthermore discuss the role of age and comorbidity in triage and highlight some principles that may seem intuitive but should not form a basis for triage. CONCLUSIONS: This overview is presented on behalf of the European Association of Neurosurgical Societies and can be used as a toolkit for neurosurgeons faced with ethical dilemmas when triaging patients in times of scarcity.

Scaling Up Global Collaborations for Neurosurgical Education and Care Capacity Development in West Africa: Are There Low-Hanging Fruits Where It Tolls?

BACKGROUND: Six decades after birth, the path to sustainable neurosurgical education and care in West Africa remains slow paced. We highlight plain sailing local attributes and global interventions for accelerated progress. METHODS: This was a 20-year study of neurosurgical practice and training status from 1999 to 2018. We prospectively evaluated development of neurosurgical units between 2009 and 2018 and compared with retrospective data both from 1999 to 2018 and from the origin of West African neurosurgery in 1962. RESULTS: The number of neurosurgeons rose from 1 in 1962 to 221 in 2018 with a mean of 3.95 neurosurgeons per year. Between 1998 and 2018, the subregional annual neurosurgeon birthrate varied significantly between 0.72 and 3.95. In 1998, 7 countries contributed to a neurosurgeon population of 26. In 2018, 13 countries contributed to a total of 221 neurosurgeons. The period 2009-2018 recorded the highest growth of neurosurgeons with a neurosurgeon birthrate of 7.5. Nigeria accounts for 51.6% (200.9 million) of the West African population and has 57% (11) of the 19 fully accredited training centers, while Ghana and Senegal account for 7.7% and 4.3% of the West African population, respectively, and each has 11% of the training centers. The 10-year unit procreativity index for the period 2009-2018 was 1.3, with Nigeria accounting for 0.7 (53.8%). CONCLUSIONS: The low unit procreativity index across West Africa, a major cause of the low neurosurgeon birthrate, can be resolved using tailored kindling and procreative strategies.

Accumulation of DNA methylation alterations in paediatric glioma stem cells following fractionated dose irradiation.

BACKGROUND: Radiation is an important therapeutic tool. However, radiotherapy has the potential to promote co-evolution of genetic and epigenetic changes that can drive tumour heterogeneity, formation of radioresistant cells and tumour relapse. There is a clinical need for a better understanding of DNA methylation alterations that may follow radiotherapy to be able to prevent the development of radiation-resistant cells. METHODS: We examined radiation-induced changes in DNA methylation profiles of paediatric glioma stem cells (GSCs) in vitro. Five GSC cultures were irradiated in vitro with repeated doses of 2 or 4 Gy. Radiation was given in 3 or 15 fractions. DNA methylation profiling using Illumina DNA methylation arrays was performed at 14 days post-radiation. The cellular characteristics were studied in parallel. RESULTS: Few fractions of radiation did not result in significant accumulation of DNA methylation alterations. However, extended dose fractionations changed DNA methylation profiles and induced thousands of differentially methylated positions, specifically in enhancer regions, sites involved in alternative splicing and in repetitive regions. Radiation induced dose-dependent morphological and proliferative alterations of the cells as a consequence of the radiation exposure. CONCLUSIONS: DNA methylation alterations of sites with regulatory functions in proliferation and differentiation were identified, which may reflect cellular response to radiation stress through epigenetic reprogramming and differentiation cues.

Effects of the growth pattern of medulloblastoma on short-term neurological impairments after surgery: results from the prospective multicenter HIT-SIOP PNET 4 study.

OBJECTIVE: Extensive resection of a tumor in the posterior fossa in children is associated with the risk of neurological deficits. The objective of this study was to prospectively evaluate the short-term neurological morbidity in children after medulloblastoma surgery and relate this to the tumor's growth pattern and to the extent of resection. METHODS: In 160 patients taking part in the HIT-SIOP PNET 4 (Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma) trial, neurosurgeons prospectively responded to questions concerning the growth pattern of the tumor they had resected. The extent of resection (gross, near, or subtotal) was evaluated using MRI. The patients' neurological status before resection and around 30 days after resection was recorded. RESULTS: Invasive tumor growth, defined as local invasion in the brain or meninges, cranial nerve, or major vessel, was reported in 58% of the patients. After surgery almost 70% of all patients were affected by one or several neurological impairments (e.g., impaired vision, impaired extraocular movements, and ataxia). However, this figure was very similar to the preoperative findings. Invasive tumor growth implied a significantly higher number of impairments after surgery (p = 0.03) and greater deterioration regarding extraocular movements (p = 0.012), facial weakness (p = 0.048), and ataxia in the arms (p = 0.014) and trunk (p = 0.025) compared with noninvasive tumor growth. This deterioration was not dependent on the extent of resection performed. Progression-free survival (PFS) at 5 years was 80% ± 4% and 76% ± 5% for patients with invasive and noninvasive tumor growth, respectively, with no difference in the 5-year PFS for extent of resection. CONCLUSIONS: Preoperative neurological impairments and invasive tumor growth were strong predictors of deterioration in short-term neurological outcome after medulloblastoma neurosurgery, whereas the extent of resection was not. Neither tumor invasiveness nor extent of resection influenced PFS. These findings support the continuation of maximal safe resection in medulloblastoma surgery where functional risks are not taken in areas with tumor invasion.