Evaluation of KIAA1549::BRAF fusions and clinicopathological insights of pilocytic astrocytomas.

BACKGROUND: Pilocytic astrocytoma (PAs) represents a significant portion of childhood primary brain tumors, with distinct histological and radiological features. The prevalence of KIAA1549::BRAF fusion in PAs has been well-established, this study aims to assess the prevalence of KIAA1549::BRAF fusions and explore their associations with tumor characteristics, radiological findings, and patient outcomes in PAs. METHODS: Histologically confirmed cases of PAs from a 5-year period were included in the study. Demographic, histopathological, and radiological data were collected, and immunohistochemistry was performed to characterize tumor markers. FISH and qRT-PCR assays were employed to detect KIAA1549::BRAF fusions. Statistical analyses were conducted to examine associations between fusion status and various other parameters. RESULTS: Histological analysis revealed no significant differences in tumor features based on fusion status. However, younger age groups showed higher fusion prevalence. Radiologically, fusion-positive cases were distributed across different tumor subtypes SE, CWE and NCWE. Survival analysis did not demonstrate a significant impact of fusion status on overall survival, however most cases with recurrence and death harboured KIAA1549::BRAF fusion. Of 200 PAs, KIAA1549::BRAF fusions were detected in 64 % and 74 % of cases via qRT-PCR and FISH, respectively. Concordance between the two platforms was substantial (86 %). CONCLUSION: KIAA1549::BRAF fusions are prevalent in PAs and can be reliably detected using both FISH and qRT-PCR assays. Cost considerations suggest qRT-PCR as a more economical option for fusion detection in routine clinical practice.

Multiple spinal extradural arachnoid cysts presenting as compressive myelopathy in a teenager: case report and literature review with special emphasis on postoperative spine deformity in the current minimally invasive era.

INTRODUCTION: Multiple synchronous spinal extradural arachnoid cysts are extremely rare in children and can lead to cord compression and disability. Multiple spinal extradural arachnoid cysts (SEDACs) in children with immature and growing spine need to be studied separately from multiple SEDACs in adults with mature and fully grown spine because of multiple surgical limitations in children (blood loss, surgery duration, long-term spinal stability after long segment exposure, etc.). MATERIAL AND METHODS: We planned a non-systematic literature review of similar cases described in literature to analyse the pattern of presentation, management, and outcome of this surgically curable disease. RESULTS: A total of 28 cases of paediatric multiple SEDACs in the age range of 5 months to 17 years and mean age of 11.54 years were analysed. Exposure was achieved by laminectomy in 9, laminoplastic laminotomy in 13, laminectomy in first surgery followed by laminoplasty in second surgery (re-exploration) in 1, hemilaminectomy in 2, and technique "not reported" in 3 children. Complete/near-complete recovery was seen in 27 (96.42%) children. Postoperative spine deformity was reported in 7 (25%) children and was progressive in 2 children during serial follow-up. CONCLUSIONS: Symptomatic multiple synchronous SEDACs in children is a rare surgically curable condition. Sincere attempt to find out a dural defect in all cysts is a very important step in multiple SEDAC surgery. Total cyst wall excision with closure of all dural defects is the gold standard treatment for symptomatic cases. Laminoplasty is preferred for excision of multiple SEDACs in children to prevent postoperative spine deformity during long-term follow-up. Long serial follow-up for postoperative spine deformity is necessary.

Long-Term Cryopreservation of Peripheral Blood Stem Cell Harvest Using Low Concentration (4.35%) Dimethyl Sulfoxide with Methyl Cellulose and Uncontrolled Rate Freezing at -80 °C: An Effective Option in Resource-Limited Settings.

Long-term cryopreservation of peripheral blood stem cells (PBSCs) is highly useful in the setting of tandem/multiple transplantations or treatment of relapse in the autologous hematopoietic stem cell transplantation (HSCT) setting. Even in allogeneic HSCT, donor lymphocyte infusions may be stored for months to years if excess stem cells are collected from donors. Cryopreservation is a delicate, complex, and costly procedure, and higher concentrations of dimethyl sulfoxide (DMSO), a commonly used cryoprotectant, can be toxic to cells and cause adverse effects in the recipient during infusions. In this study, we examined the effect of long-term cryopreservation using 4.35% DMSO (as final concentration) with methyl cellulose and uncontrolled rate freezing in a mechanical freezer (-80 °C) on the viability and colony-forming ability of CD34+ human PBSCs. For patients undergoing autologous HSCT, PBSCs were cryopreserved using DMSO (final concentration of 4.35%) with methyl cellulose. The post-thaw viability of PBSCs was determined using Trypan blue exclusion and flow cytometry-based 7-amino-actinomycin-D (FC-7AAD) methods. Concentrations of CD34+ stem cells and immune cell subsets in post-thaw PBSC harvest samples were assessed using multicolor flow cytometry, and the clonogenic potential of post-thaw stem cells was studied using a colony-forming unit (CFU) assay. CD34+ stem cell levels were correlated with the prestorage CD34 levels using the Pearson correlation test. The viability results in the Trypan blue dye exclusion method and the flow cytometry-based method were compared using Bland-Altman plots. We studied 26 PBSC harvest samples with a median cryopreservation duration of 6.6 years (range, 3.8 to 11.5 years). The median viability of post-thaw PBSCs was >80% using both methods, with a weak agreement between them (r = .03; P = .5). The median CD34+ stem cell count in the post-thaw samples was 9.13 × 106/kg (range, .44 to 26.27 × 106/kg). The CFU assay yielded a good proliferation and differentiation potential in post-thaw PBSCs, with a weak correlation between granulocyte macrophage CFU and CD34+ stem cell levels (r = .4; P = .05). Two samples that had been cryopreserved for >8 years showed low viability. Cryopreservation of PBSCs using 4.35% DMSO with methyl cellulose and uncontrolled freezing in a mechanical freezer at -80 °C allows the maintenance of long-term viability of PBSC for up to 8 years.

Brain Tumor Programs in Asia and Africa: Current Status, Challenges, and Future Perspectives.

OBJECTIVE: To assess the status of brain tumor programs in Asia and Africa and propose comprehensive evidence-based short- and long-term measures for improving the existing systems. METHODS: A cross-sectional analytical study was conducted in June 2022 by the Asia-Africa Neurosurgery Collaborative. A 27-item questionnaire was designed and distributed to gain insight into the status and future directions of brain tumor programs in Asia and Africa. Six components of brain tumor programs were identified-surgery, oncology, neuropathology, research, training, and finances-and assigned scores of 0-14. The total scores allowed subclassification of each country into levels of brain tumor program from I to VI. RESULTS: A total of 110 responses from 92 countries were received. These were subdivided into 3 groups: group 1, countries with response from neurosurgeons (73 countries); group 2, countries with no neurosurgeons (19 countries); and group 3, countries without a neurosurgeon response (16 countries). The components associated with the highest level of brain tumor program were surgery, neuropathology, and oncology. Most countries in both continents had level III brain tumor programs with a mean surgical score of 2.24. The major lag between each group was with respect to the advances in neuropathology and financial support. CONCLUSIONS: There is an urgent need to improve and develop existing and nonexistent neuro-oncology infrastructure, personnel, and logistics in countries across the continents, especially for the countries with no neurosurgeons.

Adverse Radiation Effects Following Gamma Knife Radiosurgery.

Gamma Knife Radiosurgery (GKRS) is now an established standard of treatment for the small-sized arteriovenous malformations (AVMs), meningiomas, schwannomas, metastasis, and other benign diseases. With an exponential rise in the indications for GKRS, we have witnessed an increase in the adverse radiation effects (ARE) following GKRS. The common AREs and associated risk factors following GKRS have been described for pathologies including vestibular schwannomas, arteriovenous malformations, meningiomas, and metastases based on the authors' experience, and a simplified management protocol has been provided for radiation-induced changes based on clinical and radiologic parameters. The dose, volume, location, and repeat stereotactic radiosurgery (SRS) are implied as the risk factors for ARE. Clinically symptomatic AREs require oral steroids for weeks to alleviate symptoms. In refractory cases, bevacizumab and surgical resection can be offered as a treatment modality. Appropriate dose planning strategy and hypofractionation for larger lesions help in mitigating the AREs.

Country-Made Firearm (Desi-Katta)-Related Cranial Injuries: An Institutional Experience.

Background: Approximately, 80% of civilian cranial gunshot injuries in India are mainly due to unlicensed mostly country-made guns, called the "Desi-Kattas," manufactured by the traditional gunsmiths. These injuries constitute a unique subgroup, with respect to the make and design along with the unique wound ballistics compared to the factory-made firearms. Objective: This study is aimed at defining the prognostic factors in predicting the outcomes related to cranial gunshot injuries due to these desi-kattas. Methods: Ten patients with kata-related cranial gunshot injury underwent surgical intervention at our institution, between 2014 and 2018. Their clinical status, imaging features, and outcomes were retrospectively analyzed. Results: Ten patients with kata-related gunshot injuries to the head were identified. Homicidal injuries were documented in six cases. Five had a GCS of 13-15 at presentation. Exit wounds were noted in 50% of the suicidal cases. Multilobar involvement was seen in 70% of cases, with the bullet crossing the midline in only 40% cases. Decompressive craniectomy was required in five cases. Eight patients had a Glasgow Outcome Score of four or more at 6 months of follow-up. There was one death during the follow-up period, while the other patient remains to be in vegetative state. Conclusion: The Katta-related cranial injuries constitute low-muzzle velocity injuries with the majority of the patients sustaining nonfatal injuries, especially homicidal. The presence of positive CT findings and the crossing of the bullet across the midline on CT brain predicts dismal prognosis. Optimal neurosurgical approach should consist of minimal local debridement and attain water seal dural closure.

O-Arm Assisted Anterior Odontoid Screw Fixation in Type II and Rostral Type III Odontoid Fractures: Single Center Surgical Series of 50 Patients.

Background: Accuracy of screw placement is one of the important factors necessary for adequate union in odontoid fractures with malposition rates as high as 27.2% with standard techniques. Objective: To evaluate efficacy of intraoperative O-arm assistance in improving accuracy of anterior odontoid screw placement and clinco-radiological outcome in type II and III odontoid fractures. Material and Methods: In this retrospective study, surgery consisted of anterior odontoid screw fixation under intraoperative O-arm assistance over 5 years. Demographical, clinical, radiological, operative details and postoperative events were retrieved from hospital database and evaluated for fusion and surgical outcome. Results: 50 patients (Mean age 34.6 years, SD 14.10, range: 7-70 years; 44 males and 6 females) with Type II and Type III odontoid fracture underwent O-arm assisted anterior screw placement. The mean interval between injury and surgery was 12 days (range 1-65 days). Mean operating time was 132.2 min ± SD 33.56 with average blood loss of 93 ml. ±SD 61.46. With our technique, accurate screw placement was achieved in 100% patients. At the mean follow-up of 26.4 month (SD13.75), overall acceptable fusion rate was 97.8% with non-union in 2.2% patients. Morbidity occurred in two patients; one patient developed fixation failure while other patient had nonunion which was managed with posterior C1-C2 arthrodesis. We had surgical mortality in one patient due to SAH. So overall our procedure was successful in 94% patients and among patients whose follow-up was available, acceptable fusion rates of 97.8% were achieved. Conclusion: We conclude that use of intraoperative three-dimensional imaging using O-arm for anterior odontoid screw fixation improves accuracy and leads to improved radiological and clinical outcomes. It further enables us to extend the indications of odontoid screw fixation to selected complex Type II and rostral Type III odontoid fractures.

Evaluation and Management of Nonsyndromic Craniosynostosis.

Nonsyndromic craniosynostosis (NSC) is more common than syndromic craniosynostosis and predominantly involves single suture. It affects sagittal, coronal, metopic, and lambdoid sutures in the decreasing order of frequency. A surgery for NSC is generally recommended to avoid potential neurodevelopmental delays and sequelae of raised intracranial pressure. Open calvarial vault reconstruction, strip craniectomy with/without the use of a postoperative molding helmet, strip craniectomy with spring implantations, endoscopic suture release, and cranial distraction osteogenesis are various surgical options used for NSC cases. The ideal age for intervention is 6-12 months for open procedures and 3-4 months for endoscopic approaches. The management is directed toward minimizing operative trauma and improving the neurocognitive outcome. The role of nonsurgical intervention by the use of genetic manipulation is still not a reality because of the nature of disease and time of presentation.

A Century With Craniopagus Twin Separation Surgeries: Nihilism to Optimism.

Craniopagus conjoined twins are extremely rare, reported 1 in 2.5 million live births. To date, 62 separation attempts in 69 well-documented cases of craniopagus twins have been made. Of these, 34 were performed in a single-stage approach, and 28 were attempted in a multistage approach. One or both twins died of massive intraoperative blood loss and cardiac arrest in 14 cases. We report our surgical experience with conjoined craniopagus twins (JB) with type III total vertical joining and shared circumferential/circular sinus with left-sided dominance. A brief review of the literature is also provided. In our twins, the meticulous preoperative study and planning by the multidisciplinary team consisting of 125-member, first-staged surgical separation consisted of creation of venous conduit to bypass part of shared circumferential sinus and partial hemispheric disconnection. Six weeks later, twin J manifested acute cardiac overload because of one-way fistula development from blocked venous bypass graft necessitating emergency final separation surgery. Unique perioperative issues were abnormal anatomy, hemodynamic sequelae from one-way fistula development after venous bypass graft thrombosis, cardiac arrest after massive venous air embolism requiring prolonged cardiopulmonary resuscitation, and return of spontaneous circulation at 15 minutes immediately after separation. This is the first Indian craniopagus separation surgery in a complex total vertical craniopagus twin reported by a single-center multidisciplinary team. Both twins could be sent home, but one remained severely handicapped. Adequate perioperative planning and multidisciplinary team approach are vital in craniopagus twin separation surgeries.

First Successful Separation of Craniopagus Twins in India-Plastic Surgical Considerations.

Separation of total vertical craniopagus with shared venous sinuses poses multiple challenges. Provision of soft-tissue cover to the exposed brains at the time of total separation is one of them, due to the large size of the defect and paucity of local tissues. Staged separation of twins is advised with partial venous and parenchymal disconnection in the first stage and total separation in the second stage. Tissue expanders are inserted in the first stage, and second stage planned to coincide with the period of adequate expansion. In the child being reported, emergency second stage was done due to the deteriorating general condition of the children. Left with inadequate expanded skin, the critical defect in a twin was managed with bilateral trapezius myocutaneous flaps. High ionotropic support of the postoperative period resulted in superficial necrosis of the flap, which was managed by debridement, allograft application and autograft later. Both twins had well-healed wounds by 3 months.

Lessons learned during covid-19 pandemic, a worldwide survey: evolution of global neurosurgical practice.

BACKGROUND: During the COVID-19 pandemic, a multitude of surveys have analyzed the impact virus spreading on the everyday medical practice, including neurosurgery. However, none have examined the perceptions of neurosurgeons towards the pandemic, their life changes, and the strategies they implemented to be able to deal with their patients in such a difficult time. METHODS: From April 2021 to May 2021 a modified Delphi method was used to construct, pilot, and refine the questionnaire focused on the evolution of global neurosurgical practice during the pandemic. This survey was distributed among 1000 neurosurgeons; the responses were then collected and critically analyzed. RESULTS: Outpatient department practices changed with a rapid rise in teleservices. 63.9% of respondents reported that they have changed their OT practices to emergency cases with occasional elective cases. 40.0% of respondents and 47.9% of their family members reported to have suffered from COVID-19. 56.2% of the respondents reported having felt depressed in the last 1 year. 40.9% of respondents reported having faced financial difficulties. 80.6% of the respondents found online webinars to be a good source of learning. 47.8% of respondents tried to improve their neurosurgical knowledge while 31.6% spent the extra time in research activities. CONLCUSIONS: Progressive increase in operative waiting lists, preferential use of telemedicine, reduction in tendency to complete stoppage of physical clinic services and drop in the use of PPE kits were evident. Respondents' age had an impact on how the clinical services and operative practices have evolved. Financial concerns overshadow mental health.

An investigation to the prolonged requirement (>7 days) of vasopressors in cervical spinal cord injury patients-a retrospective analysis.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: The primary aim was to identify the number of patients requiring vasopressors beyond the first week of cervical spinal cord injury (SCI). Secondary objectives were to note the type, duration and doses of vasopressors and any association between prolonged vasopressors use and outcome. SETTING: Neurosurgical intensive care of a tertiary trauma care centre. METHODS: After Ethical approval we retrospectively collected the data of patients of isolated cervical SCI admitted to neurosurgical intensive care from January to December 2017. Vasopressor requirement for sepsis or cardiac arrest was excluded. RESULTS: Out of 80 patients analysed, 54 (67.5%) received vasopressors. The prolonged requirement of vasopressors was observed in 77.7%. Our preferred agent was dopamine (64.8%). We found out that longer requirement (in days) of high dose of dopamine was associated with higher survival (p = 0.03). CONCLUSION: Our results describe a significant portion of cervical SCI patients need ongoing vasopressor to maintain a mean arterial pressure >65 mm of Hg beyond first week. We observed patients who required longer duration of high dose dopamine had a higher chance of survival suggesting some unknown mechanism of high dose of dopamine. This is first such observation, further studies are needed to substantiate.

Improved protocol for plasma microRNA extraction and comparison of commercial kits.

INTRODUCTION: MicroRNAs are small, non-coding RNA molecules that are becoming popular biomarkers in several diseases. However, their low abundance in serum/plasma poses a challenge in exploiting their potential in clinics. Several commercial kits are available for rapid isolation of microRNA from plasma. However, reports guiding the selection of appropriate kits to study downstream assays are scarce. Hence, we compared four commercial kits to evaluate microRNA-extraction from plasma and provided a modified protocol that further improved the superior kit's performance. MATERIALS AND METHODS: We compared four kits (miRNeasy Serum/Plasma, miRNeasy Mini Kit from Qiagen; RNA-isolation, and Absolutely-RNA MicroRNA Kit from Agilent technologies) for quality and quantity of microRNA isolated, extraction efficiency, and cost-effectiveness. Bioanalyzer-based Agilent Small RNA kit was used to evaluate quality and quantity of microRNA. Extraction efficiency was evaluated by detection of four endogenous control microRNA using real-time-PCR. Further, we modified the manufacturer's protocol for miRNeasy Serum/Plasma kit to improve yield. RESULTS: miRNeasy Serum/Plasma kit outperformed the other three kits in microRNA-quality (P < 0.005) and yielded maximum microRNA-quantity. Recovery of endogenous control microRNA i.e. hsa-miR-24-3p, hsa-miR-191-5p, hsa-miR-423-5p and hsa-miR-484 was higher as well. Modification with the inclusion of a double elution step enhanced yield of microRNA extracted with miRNeasy Serum/Plasma kit significantly (P < 0.001). CONCLUSION: We demonstrated that miRNeasy Serum/Plasma kit outperforms other kits and can be reliably used with a limited plasma quantity. We have provided a modified microRNA-extraction protocol with improved microRNA output for downstream analyses.