Developing a non-cadaveric brain tumour surgery lab in resource-constrained settings.

OBJECTIVE: To develop the country's first brain tumour surgery lab in resource-constrained settings, for training young neurosurgeons and residents. METHODS: A workshop was developed using mixed-fidelity models for assessing and training a participant's psychomotor skills, hand-eye coordination, and teaching the principles of brain tumour surgery. Affordable noncadaveric models were used to compare and contrast the benefit of each teaching model. Within the existing space for wet labs at our institution, 8 different dissection stations were set up with adequate space for 2 people to work at a time. Each station was equipped with an operating room-Caliber microscope, a lighting system and a camera linked to a screen and high-powered electric drills and basic surgical equipment. RESULTS: Our team was able to develop and use 3D-printed skull models and animal brain models for training in complex approaches and craniotomy. CONCLUSIONS: Surgical simulation training, in a cost-effective manner, provides the benefit of training residents and students in neurosurgical techniques in a safe, controlled environment leading to improvement in skills and technique.

The need for economic evaluations for neuro-oncology in low- and middleincome: the Pakistan perspective.

The incidence and prevalence of brain tumours have steadily increased within low- and middle-income countries, similar to patterns seen in high-income countries. In addition to the epidemiological landscape of brain tumours in Pakistan, it is important to consider the economics of brain tumour diagnosis and management to inform policy on neuro-oncological healthcare service delivery. The challenges associated with conducting economic evaluations in LMICs include the ability to receive funding for country-specific estimates, dearth of existing data and methodological development, and the need for investment in economic evaluations of health. Economic evaluations are most useful when funding support is given to country-specific initiatives to allocate resources. Cost and cost components must also be meticulously collected to enable accurate calculations of economic evidence for the decision-making process. To put neuro-oncological care at the forefront of the national health agenda, it is crucial for vigorous epidemiological and economic evidence to be available for policymakers.

Role of neurosurgeons In strengthening paediatric neuro-oncology In low- and middle-income countries: a narrative review with case examples.

Paediatric neuro-oncology in low- and middle-income countries (LMICs) accounts for a significant proportion of cancer-related mortalities in this age group. The current dearth of structured paediatric neurosurgery training programmes in LMICs requires multidisciplinary coordination; neurosurgeons play certain key roles, as discussed in this article, in ensuring safe and effective care for paediatric neuro-oncology patients. This document intends to elaborate through illustrative cases of the technical and structural nuances required by neurosurgeons in LMICs to provide appropriate surgical care.

Consensus guidelines for the management of vestibular schwannoma for lowand middle-income countries.

Vestibular Schwannoma (VS), previously known as acoustic neuroma, constitutes the majority of tumours found in the cerebellopontine angle (CPA). Most guidelines for managing CPA tumours have been developed by high-income countries (HICs). However, these guidelines often fall short in addressing the unique challenges encountered in low- and middle-income countries (LMICs), such as Pakistan. In LMICs, issues related to a limited healthcare workforce, inadequate infrastructure, and constrained financial resources hinder the effective implementation of these HIC-derived guidelines. Additionally, it has been observed that VS tends to present at a larger size in LMICs compared to HICs. Given that VS is the predominant type of CPA tumour and other types are covered under separate guidelines, this article aims to provide practical, contextspecific recommendations for the screening, diagnosis, and management of Vestibular Schwannoma in LMIC settings. Our focus is to bridge the gap in care strategies and adapt them to the resource constraints and clinical realities of LMICs.

Developing neuro-oncology clinical trials in low- and middle-income countries: a scoping review of the current literature.

Low- and middle-income countries (LMICs) have historically been under-represented in clinical trials, leading to a disparity in evidence-based recommendations for the management of neurooncological conditions. To address this knowledge gap, we conducted a scoping review to assess the current literature on clinical trials in neuro-oncology from LMICs. The eligibility criteria for inclusion in this review included clinical trials registered and conducted with human subjects, with available English language text or translation, and focussed on neuro-oncological cases. The literature search strategy captured 408 articles, of which 61 met these criteria, with a significant number of randomised controlled trials from specific LMICs. The review found that LMIC clinical trials have contributed significantly to understanding surgical, chemotherapeutic, and radiation therapy interventions for brain tumours, paediatric cancers, and the repurposing of drugs as new targets in neuro-oncology. These findings highlight the potential for expanding clinical trials research in neuro-oncology in LMICs, which may significantly impact global understanding and management of these conditions, particularly from diverse populations from the global south.

Consensus guidelines for the management of intracranial metastases for low- and middle-income countries.

Metastatic tumours are among the most common types of brain tumours. However, in low- and middle-income countries (LMICs), the numbers are considerably lower. This does not necessarily indicate a decreased incidence but rather points to decreased survival rates or limited access to healthcare. The challenge of achieving better outcomes, along with associated costs and resource constraints, often hinders the effective management of brain metastasis. Even in cases where localised disease can potentially be managed to improve survival, these challenges persist. The purpose of these guidelines is to address these challenges and outline a management strategy within the context of LMICs.

Consensus guidelines for the management of intracranial ependymoma for low- and middle-income countries.

This paper presents comprehensive consensus guidelines for the management of intracranial ependymoma, neoplasms arising from ependymal cells in the central nervous system's ventricular system, in low- and middleincome countries (LMICs). Acknowledging the distinct epidemiological patterns of ependymomas, notably their higher incidence in paediatric patients, and variable survival rates, these guidelines emphasize tailored management approaches for different age groups. An expert panel, comprising specialists in neuro-oncology, convened to address gaps in diagnosis and management within LMICs, considering the varying clinical presentation based on tumour size and location. Emphasizing surgical intervention as the cornerstone of treatment, the guidelines also address challenges such as intraoperative bleeding and tumour location impacting complete resection. The role of molecular subgrouping in stratifying treatment and predicting prognosis is highlighted, alongside a careful consideration of radiotherapy timing, dose, and volume based on risk factors. Chemotherapy's role, especially in paediatric cases, is explored. The paper synthesizes current research and expert opinions, including the need for standardisation, genetic testing, and exploration of less invasive treatment modalities, to address the unique healthcare infrastructure challenges in LMICs. The guidelines also emphasize multidisciplinary teams, aiming to bridge the care gap between high-income countries and LMICs, and improve survival rates and quality of life for patients with intracranial ependymoma. This article serves as a valuable resource for clinicians, researchers, and policymakers in Pakistan and beyond, facilitating the development of evidence-based strategies in diverse healthcare settings.

Consensus guidelines for the management of craniopharyngioma in low- and middle-income countries.

Craniopharyngiomas are benign, extra-axial epithelial tumours originating from the pituitary stalk, impacting areas such as the hypothalamus, optic chiasm, and various cranial nerves. These tumours present unique surgical challenges due to their proximity to critical neurovascular structures. Management typically involves maximal safe resection as the primary approach. However, in low- and middle-income countries (LMICs), factors like late presentation, higher risks of endocrine and visual complications, frequent recurrence, and potential for incomplete resection complicate treatment. These challenges are exacerbated by limited access to specialised expertise and surgical equipment, increasing the risk of damage during surgery compared to High- Income Countries. This manuscript outlines management guidelines tailored for LMICs, emphasizing that a combination of surgical resection and chemoradiation therapy, as advised by a neuro-oncology tumour board, often yields the best outcomes.

Role of Proton Beam Therapy in Spinal Chordomas: A Narrative Review of The Literature.

Chordomas are rare malignant neoplasms arising from vestigial remnants of the embryonic notochord. Approximately 55-70% of chordomas develop within the vertebral column. Their affinity to develop within the bones of the axial skeleton and propensity to locally invade and recur makes them challenging candidates for complete surgical excision. Adjuvant therapies are hence necessary to improve outcomes; for which chemotherapy has been observed to be largely ineffective, owing to the tumour being resistant to it. Radiotherapy is the current adjuvant therapy of choice for chordoma management. Over the years, proton beam therapy (PBT) has been the subject of medical attention, given the dosimetric benefits it confers over traditional radiotherapy, allowing more concentrated radiation to be given to the target of interest and reducing damage to surrounding normal tissue. A review of the current literature reveals PBT offers significantly better outcomes when used as an adjuvant to maximal surgical resection rather than as a definitive therapy.

Sbno1 mediates cell-cell communication between neural stem cells and microglia through small extracellular vesicles.

BACKGROUND: Neural stem cells (NSCs) play a crucial role in the progress of ischemic stroke. Research on zebrafish embryonic demonstrates an association between Strawberry Notch 1 (Sbno1) and central nervous system development. However, the regulation and underlying mechanism of Sbno1 in NSCs have not been studied yet. Here, we investigated the role and the mechanism of Sbno1 in NSCs development and the potential therapeutic value of Sbno1 in ischemic stroke. METHODS: Adeno-associated virus (AAV) was used for overexpression or knockdown of Sbno1 in vitro or in vivo. A mouse model of MCAO was established to evaluate the neuroprotective effects of AAV-Sbno1, including balance beam test, rotarod test, and strength evaluation. H&E and immunofluorescence assessed neuronal impairment. Western blot and RT-qPCR were used to detect the expression of Sbno1 and its downstream target genes. RNA-seq and western blot were performed to explore further molecular mechanisms by which Sbno1 promoted endogenous repair of NSCs and macrophages M2 polarization. CCK8 was conducted to assess the effects of Sbno1 on NSCs proliferation. The impact of Sbno1 on NSCs apoptosis was evaluated by flow cytometry. NSCs derived from small extracellular vesicles (sEV) were obtained using ultracentrifugation and identified through nanoparticle tracking analysis (NTA) and western blot analysis. RESULTS: Our results showed that Sbno1 is highly expressed in the central nervous system, which plays a crucial role in regulating the proliferation of NSCs through the PI3k-Akt-GSK3ß-Wnt/ß-catenin signaling pathway. In addition, with overexpression of Sbno1 in the hippocampus, post-stroke behavioral scores were superior to the wild-type mice, and immunofluorescence staining revealed an increased number of newly generated neurons. sEV released by NSCs overexpressing Sbno1 inhibited neuroinflammation, which mechanistically impaired the activation of the microglial NF-κB and MAPK signaling pathways. CONCLUSIONS: Our studies indicate that sbno1 promotes the proliferation of NSCs and enhances endogenous repairing through the PI3k-Akt-GSK3ß-Wnt/ß-catenin signaling pathway. Additionally, NSCs overexpressing sbno1 improve ischemic stroke recovery and inhibit neuroinflammation after ischemia by sEV through the MAPK and NF-κB signaling pathways.

Effects of high-definition tDCS targeting individual motor hotspot with EMG-driven robotic hand training on upper extremity motor function: a pilot randomized controlled trial.

BACKGROUND: Delivering HD-tDCS on individual motor hotspot with optimal electric fields could overcome challenges of stroke heterogeneity, potentially facilitating neural activation and improving motor function for stroke survivors. However, the intervention effect of this personalized HD-tDCS has not been explored on post-stroke motor recovery. In this study, we aim to evaluate whether targeting individual motor hotspot with HD-tDCS followed by EMG-driven robotic hand training could further facilitate the upper extremity motor function for chronic stroke survivors. METHODS: In this pilot randomized controlled trial, eighteen chronic stroke survivors were randomly allocated into two groups. The HDtDCS-group (n = 8) received personalized HD-tDCS using task-based fMRI to guide the stimulation on individual motor hotspot. The Sham-group (n = 10) received only sham stimulation. Both groups underwent 20 sessions of training, each session began with 20 min of HD-tDCS and was then followed by 60 min of robotic hand training. Clinical scales (Fugl-meyer Upper Extremity scale, FMAUE; Modified Ashworth Scale, MAS), and neuroimaging modalities (fMRI and EEG-EMG) were conducted before, after intervention, and at 6-month follow-up. Two-way repeated measures analysis of variance was used to compare the training effect between HDtDCS- and Sham-group. RESULTS: HDtDCS-group demonstrated significantly better motor improvement than the Sham-group in terms of greater changes of FMAUE scores (F = 6.5, P = 0.004) and MASf (F = 3.6, P = 0.038) immediately and 6 months after the 20-session intervention. The task-based fMRI activation significantly shifted to the ipsilesional motor area in the HDtDCS-group, and this activation pattern increasingly concentrated on the motor hotspot being stimulated 6 months after training within the HDtDCS-group, whereas the increased activation is not sustainable in the Sham-group. The neuroimaging results indicate that neural plastic changes of the HDtDCS-group were guided specifically and sustained as an add-on effect of the stimulation. CONCLUSIONS: Stimulating the individual motor hotspot before robotic hand training could further enhance brain activation in motor-related regions that promote better motor recovery for chronic stroke. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov (ID NCT05638464).

Judicious and evidence-based use of radiosurgery - recommendations for low-middle income countries.

Surgical removal remains the primary treatment for most brain tumours. However, radiosurgery presents an effective, less invasive alternative or additional treatment for certain types. Our goal was to explore radiosurgery's roles in treating various brain tumours, focussing on its application in low- and middle-income countries (LMICs). We reviewed all relevant systematic reviews, metaanalyses, and guidelines to determine the most effective radiosurgical approaches. Additionally, we consulted a panel of experts with over ten years of experience in LMICs, such as Pakistan. For brain tumours, stereotactic radiosurgery should generally follow a confirmed histopathological diagnosis. Exceptions include tumours identified through Magnetic Resonance Imaging (MRI), like Vestibular Schwannoma (VS), pre-diagnosed Neurofibromatosis type 2 (NF2), multiple typical meningiomas, and metastases with a known histology from another site. While radiosurgery is gaining traction as a primary and adjunct treatment in some LMICs, the lack of regional guidelines, trained personnel, and collaboration among specialists hinders its wider adoption. Addressing these gaps is crucial for expanding radiosurgical care in these regions.

Consensus guidelines for the management of adult low-grade gliomas for low and middle-income countries.

Low-grade gliomas (LGG) are brain tumors of glial cells origin. They are grade 1 and grade 2 tumors according to the WHO classification. Diagnosis of LGG is made through imaging, histopathological analysis, and use of molecular markers. Imaging alone does not establish the grade of the tumor and thus a histopathological examination of tissue is crucial in establishing the definite histopathological diagnosis. Clinical presentation varies according to the location and size of the tumor. Surgical resection is strongly recommended in LGG over observation to improve overall survival as surgery leads to greater benefit due to progression-free survival. Radiation has shown benefits in LGG patients in randomized controlled trials and chemotherapy with temozolomide has also shown good results. This paper covers the principles of low-grade gliomas management and summarizes the recommendations for the LMICs.

Consensus guidelines for the management of primary supra-tentorial intraventricular tumour for low- and middle-income countries.

Almost any primary or metastatic brain tumour can manifest in intraventricular (IV) locations. These tumours may either originate within the ventricular system or extend into the IV space through growth. Such neoplasms represent a broad spectrum, with supratentorial IV tumours forming a heterogeneous group. This group includes primary ependymal tumours, central neurocytomas, choroid plexus tumours, and notably, meningiomas, as well as a variety of non-neoplastic, benign, glial, and metastatic lesions that can secondarily invade the IV compartment. Often presenting with nonspecific symptoms, these tumours can lead to delayed medical attention. The diversity in potential diagnoses, combined with their deep and complex locations, poses significant management challenges. This paper aims to delineate optimal management strategies, underscoring the importance of multidisciplinary care, especially in settings with limited resources, to effectively navigate the complexities associated with treating intraventricular brain tumours.

Consensus guidelines for the management of pediatric medulloblastoma in low and middle-income countries.

The management of medulloblastoma, a pediatric brain tumor, has evolved significantly with the advent of genomic subgrouping, yet morbidity and mortality remain high in LMICs like Pakistan due to inadequate multidisciplinary care infrastructure. This paper aims to establish evidence-based guidelines tailored to the constraints of such countries. An expert panel comprising neuro-oncologists, neurosurgeons, radiologists, radiation oncologists, neuropathologists, and pediatricians collaborated to develop these guidelines, considering the specific challenges of pediatric brain tumor care in Pakistan. The recommendations cover various aspects of medulloblastoma treatment, including pre-surgical workup, neurosurgery, neuropathology, chemotherapy, radiation therapy, and supportive care. They offer both minimum required and additional optional protocols for more advanced centers, ensuring comprehensive patient management with attention to complications and complexities encountered in Pakistan. The paper's consensus guidelines strive for uniformity in healthcare delivery and address significant gaps in diagnosis, treatment, and follow-up of pediatric medulloblastoma patients.

Medial Prefrontal Cortex Stimulation Reduces Retrieval-Induced Forgetting via Fronto-parietal Beta Desynchronization.

The act of recalling memories can paradoxically lead to the forgetting of other associated memories, a phenomenon known as retrieval-induced forgetting (RIF). Inhibitory control mechanisms, primarily mediated by the prefrontal cortex, are thought to contribute to RIF. In this study, we examined whether stimulating the medial prefrontal cortex (mPFC) with transcranial direct current stimulation modulates RIF and investigated the associated electrophysiological correlates. In a randomized study, 50 participants (27 males and 23 females) received either real or sham stimulation before performing retrieval practice on target memories. After retrieval practice, a final memory test to assess RIF was administered. We found that stimulation selectively increased the retrieval accuracy of competing memories, thereby decreasing RIF, while the retrieval accuracy of target memories remained unchanged. The reduction in RIF was associated with a more pronounced beta desynchronization within the left dorsolateral prefrontal cortex (left-DLPFC), in an early time window (<500 ms) after cue onset during retrieval practice. This led to a stronger beta desynchronization within the parietal cortex in a later time window, an established marker for successful memory retrieval. Together, our results establish the causal involvement of the mPFC in actively suppressing competing memories and demonstrate that while forgetting arises as a consequence of retrieving specific memories, these two processes are functionally independent. Our findings suggest that stimulation potentially disrupted inhibitory control processes, as evidenced by reduced RIF and stronger beta desynchronization in fronto-parietal brain regions during memory retrieval, although further research is needed to elucidate the specific mechanisms underlying this effect.

Surviving the Storm: Cardiac Tamponade and Effusive Constrictive Pericarditis Complicated by Pericardial Decompression Syndrome Induced by COVID-19 Infection in the Setting of Newly Diagnosed Acute Myeloid Leukemia (AML).

Coronavirus disease 2019 (COVID-19)-induced pericarditis and pericardial myocarditis are common entities; however, the development of pericardial effusion post-COVID-19 infection has only been reported in about 5% of cases. Rapid and acute progression to pericardial tamponade is uncommon, and progression to effusive constrictive pericarditis (ECP) and pericardial decompression syndrome (PDS) is an even rarer phenomenon. We describe these phenomena in this report to raise awareness and aid clinicians in the early diagnosis and management of these conditions. We report a case of a 45-year-old female with a past medical history of recent COVID-19 infection, uncontrolled diabetes mellitus, and hypertension who presented with severe chest pain, which was determined to be acute pericarditis post-COVID-19 infection. The patient developed a large pericardial effusion leading to cardiac tamponade within one day of initial presentation. Urgent pericardiocentesis was performed but was complicated by rapid decompensation of the patient, which has been assumed to be ECP following pericardiocentesis and PDS.  Close monitoring of acute pericarditis with pericardial effusion is required in these patients for the early detection of cardiac tamponade, which requires urgent pericardiocentesis. Judicious post-pericardiocentesis follow-up is also required for the early diagnosis of conditions such as ECP and PDS. These cases are generally managed symptomatically, but in cases of severe ECP syndrome, pericardial stripping may be required.

Proposed novel classification of circumscribed Lower-Grade Gliomas (cLGG) vs. infiltrating Lower-Grade Gliomas (iLGG): Correlations of radiological features and clinical outcomes.

Purpose: We hypothesize that lower grade gliomas (LGG) can be identified and classified into two distinct subtypes: radiologically circumscribed Lower-Grade Gliomas (cLGG) and infiltrating Lower-Grade Gliomas (iLGG) based on radiological parameters and that these two different subtypes behave differently in terms of clinical outcomes. Methods: We conducted a retrospective cohort study on surgical patients diagnosed with lower grade glioma over five years. Patient records and MRIs were reviewed, and neurosurgeons classified tumors into cLGG and iLGG groups. Results: From the 165 patients in our cohort, 30 (18.2%) patients were classified as cLGG and 135 (81.8%) patients were classified as iLGG Mean age in cLGG was 31.4 years while mean age in iLGG was 37.9 years (p = 0.004). There was significant difference in mean blood loss between cLGG and iLGG groups (270 and 411 ml respectively, p = 0.020). cLGG had a significantly higher proportion of grade II tumors (p < 0.001). The overall mean survival time for the iLGG group was 14.96 ± 1.23 months, and 18.77 ± 2.72 months for the cLGG group. In univariate cox regression, the survival difference between LGG groups was not significant (HR = 0.888, p = 0.581), however on multivariate regression cLGG showed a significant (aHZ = 0.443, p = 0.015) positive correlation with survival. Intense contrast enhancement (HZ = 41.468, p = 0.018), blood loss (HZ = 1.002, p = 0.049), and moderately high Ki-67 (HZ = 4.589, p = 0.032) were also significant on univariate analyses.Conclusion: cLGG and iLGG are radiologically distinct groups with separate prognoses, surgical experience, and associations.

Successful use of a patient specific 3D-printed biomodel as surgical guide for excision of juvenile nasopharyngeal angiofibroma extending to skull base: A case report.

Background: 3-Dimensional (3D) printing has proven its role in various fields. Recently, 3D printing has also been introduced in the otolaryngology domain. The nasopharynx, paranasal sinuses, and the anterior skull base have a complex anatomy. Critical structures must be delicately protected and preserved during a surgical procedure. It is, therefore, very important for the surgeon to have an excellent spatial understanding of the complex surgical field that is being traversed. Case Description: Our case is of a 19-year-old male with a 2-month history of recurrent epistaxis, nasal blockage, and headache. Based on the computed tomography scan and the clinical presentation, the patient was diagnosed with juvenile nasopharyngeal angiofibroma. The patient underwent angioembolization of the tumor followed by endoscopic surgical resection. The patient remained stable postoperatively and demonstrated a good recovery in the follow-up visit with no signs of cranial deficits. This case report highlights the use of a patient-specific 3D-printed biomodel to visualize this rare tumor of the nasopharynx. The benefits of using the model in surgical planning, patient education, and resident training are reported. We found that the ability to visualize the tumor on a tangible model, viewing its actual size in relation to the adjacent anatomy and all the structures associated with it, greatly enhances the surgeon's capacity to tackle such a difficult tumor endoscopically. Conclusion: Incorporating 3D-printed biomodels in surgical practice should result in improved outcomes for the patients.