Postoperative Seizure Control in Adult Diffuse Insular Gliomas Presenting with Seizures: A Retrospective Single-Center Experience and Proposal of a Novel Risk Scoring System.

Background: Studies on insular gliomas (IGs) generally focus on the oncological endpoints with a relative scarcity of literature focusing on the seizure outcomes. Objectives: To study the predictors of long-term postoperative seizure control in IG and propose a novel risk scoring system. Methods: Histopathologically proven, newly diagnosed adult IGs (>18 years) operated over a 10-year period were studied for postoperative seizure control as per International League Against Epilepsy (ILAE) grades at 6 weeks and at last follow-up (minimum of 6 months, median 27 months). Logistic regression analysis was performed and regression coefficients with nearest integers were used to build a risk prediction model. Receiver operator curve (ROC) analysis determined the predictive accuracy of this model. Results: The 6-week postoperative seizure freedom dropped to 41% at the last follow-up. The seizure-free group lived longer (100.69 months, 95% CI = 84.3-116.99 (60%)) than those with persistent postoperative seizures (27.92 months, 95% CI = 14.99-40.86). Statistically significant predictors (preoperative seizure control status, extent of resection, tumor extension to temporal lobe, and lack of postoperative adjuvant therapy) were used to compute a risk score, the score ranging from 0 to 9. A score of four most optimally distinguished the risk of postoperative seizures with an area under the ROC of 91.4% (95% CI: 84.1%, 98.7%, P < 0.001). Conclusion: In our experience, around 60% of patients obtained seizure freedom after surgery, which reduces over time. Control of seizures paralleled survival outcomes. Our proposed scoring system may help tailor management strategies for these patients.

Deficiency of the minor spliceosome component U4atac snRNA secondarily results in ciliary defects in human and zebrafish.

In the human genome, about 750 genes contain one intron excised by the minor spliceosome. This spliceosome comprises its own set of snRNAs, among which U4atac. Its noncoding gene, RNU4ATAC, has been found mutated in Taybi-Linder (TALS/microcephalic osteodysplastic primordial dwarfism type 1), Roifman (RFMN), and Lowry-Wood (LWS) syndromes. These rare developmental disorders, whose physiopathological mechanisms remain unsolved, associate ante- and post-natal growth retardation, microcephaly, skeletal dysplasia, intellectual disability, retinal dystrophy, and immunodeficiency. Here, we report bi-allelic RNU4ATAC mutations in five patients presenting with traits suggestive of the Joubert syndrome (JBTS), a well-characterized ciliopathy. These patients also present with traits typical of TALS/RFMN/LWS, thus widening the clinical spectrum of RNU4ATAC-associated disorders and indicating ciliary dysfunction as a mechanism downstream of minor splicing defects. Intriguingly, all five patients carry the n.16G>A mutation, in the Stem II domain, either at the homozygous or compound heterozygous state. A gene ontology term enrichment analysis on minor intron-containing genes reveals that the cilium assembly process is over-represented, with no less than 86 cilium-related genes containing at least one minor intron, among which there are 23 ciliopathy-related genes. The link between RNU4ATAC mutations and ciliopathy traits is supported by alterations of primary cilium function in TALS and JBTS-like patient fibroblasts, as well as by u4atac zebrafish model, which exhibits ciliopathy-related phenotypes and ciliary defects. These phenotypes could be rescued by WT but not by pathogenic variants-carrying human U4atac. Altogether, our data indicate that alteration of cilium biogenesis is part of the physiopathological mechanisms of TALS/RFMN/LWS, secondarily to defects of minor intron splicing.

Anterior Skull Base Meningioma: Surgical Approach and Complication Avoidance.

Introduction Endoscopic endonasal approach (EEA) and keyhole transcranial approaches (TCAs) are being increasingly used in anterior skull base meningioma (ASBM) surgery. Objective We compare tumor resection rates and complication profiles of EEA and supraorbital keyhole approach (SOKHA) with conventional TCAs. Methods Fifty-four patients with ASBM (olfactory groove meningioma [OGM], n = 19 and planum sphenoidale/tuberculum sellae meningioma [PSM/TSM], n = 35) operated at a single center over 7 years were retrospectively analyzed. Results The overall rate of gross total resection (GTR) was higher in OGM (15/19, 78.9%) than PSM-TSM group (23/35, 65.7%, p = 0.37). GTR rate with OGM was 90% and 75% with TCA and EEA. Death ( n = 1) following medical complication (TCA) and cerebrospinal fluid leak requiring re-exploration ( n = 2, one each in TCA and EEA) accounted for the major complications in OGM. For the PSM/TSM group, the GTR rates were 73.3% ( n = 11/15), 53.8% ( n = 7/13), and 71.4% ( n = 5/7) with TCA, EEA, and SOKHA, respectively. Seven patients (20%) of PSM-TSM developed major postoperative complications including four deaths (one each in TCA and SOKHA, and two in EEA groups) and three visual deteriorations. Direct and indirect vascular complications were common in lesser invasive approaches to PSM-TSM especially if the tumor has encased intracranial arteries. Conclusion No single approach is applicable to all ASBMs. TCA is still the best approach to obtain GTR but has tissue trauma-related problems. SOKHA may be a good alternative to TCA in selected PSM-TSMs, while EEA may be an alternate option in some OGMs. A meticulous patient selection is needed to derive reported results of EEA for PSM-TSM.

"Undercutting of the corresponding rib": a novel technique of increasing the length of donor in intercostal to musculocutaneous nerve transfer in brachial plexus injury.

Intercostal nerves (ICN) are often utilized as donors for various neurotization procedures in brachial plexus injuries. ICN to musculocutaneous nerve (MCN) transfer is usually a standard in pan brachial plexus injuries, in order to restore flexion at the elbow. A tensionless co-aptation of the donor-recipient nerves often necessitates either a distal dissection of the ICNs where the number of fascicles is rather low or a proximal dissection, often at the cost of dissection of the serratus anterior digitation with a risk of later fibrosis and adhesion. We report two cases of pan brachial plexus injuries where ICN-MCN transfer was performed to restore elbow function. These patients underwent clinical and electrodiagnostic evaluation before surgery. We used the standard technique of harvesting ICNs 3-5, with our technical modification of "undercutting of rib" for increasing the donor length. The procedure was applied in two patients with pan brachial plexus injury (mean age = 23). Mean duration since the injury to surgery was ten months. Both patients underwent tensionless anastomosis with a combination of suture and fibrin glue co-aptation. While one patient had some improvement in elbow flexion, another one was under active rehabilitation protocol during follow-up. We found that undercutting of the ribs near serratus digitations can allow mobilization of the ICN from its groove, which in turn lengthens the donor nerve length without violating the serratus anterior digitations and without too anterior dissection of the nerve. It can be a viable option when a tensionless co-aptation at the axilla is otherwise not feasible intraoperatively.

Insular glioblastoma: surgical challenges, survival outcomes and prognostic factors.

BACKGROUND: Insular gliomas are unique, challenging and evoke a lot of interest amongst neurosurgeons. Publications on insular glioma generally focus on the surgical intricacies and extent of resection pertaining to the low-grade gliomas. Insular glioblastomas (iGBM) have not been analysed separately before. METHODS: Histologically proven WHO grade IV gliomas involving the insula over a 9-year period were studied. Their clinical presentation, radiological features, surgical findings and survival outcomes were assessed. Statistical methods were used to determine the favourable predictors of survival. RESULTS: Out of 27 patients (M:F = 2.9:1), 18 (66%) patients had a tumour extension beyond the insula, 10 (37%) of whom had basal ganglia involvement. Total, near total and subtotal excisions were performed in 7 (26%), 9 (33%) and 11 (40.7%) patients, respectively. Twenty-three patients had glioblastoma, while four had gliosarcoma. IDH mutation was negative in six of the seven patients where it was done. Median overall survival was 5 months. Multivariate analysis showed that a female gender (p = 0.013), seizures in the preoperative period (p = 0.048) and completion of adjuvant therapy (p = 0.003) were associated with a longer survival. CONCLUSION: Insular glioblastomas have a poor prognosis. Insular location and certain tumour characteristics often limit the extent of resection of iGBMs. Moreover, postoperative complications sometimes negate the advantages of a radical resection. A female gender, presentation with seizures and completion of adjuvant chemoradiotherapy appear to be good prognostic factors.

An Institutional Experience and Literature Review on Iatrogenic Major Vascular Injury in Neurosurgery: Proposal of a Management Algorithm.

Background: Major vessel injury is among the most dreaded complications of any neurosurgical procedure. Once intraoperatively tamponaded, it can present in the form of pseudoaneurysm, dissecting aneurysm or complete occlusion of vessel. These injuries are often associated with very high morbidity and mortality. The literature available on this topic is limited and our understanding remains limited. Objective: In this article, we present our surgical experience with iatrogenic aneurysms and present a review of literature. Methods and Material: We conducted a retrospective analysis of all patients with major vessel injury during surgery from a prospectively maintained database from January 2012 to February 2020. Results: A total of 15 patients developed iatrogenic aneurysms following a major vessel injury during various neurosurgical procedures. The most common vessel injured was vertebral artery (n = 9) in craniovertebral junction (CVJ) anomalies and ossification of posterior longitudinal ligament (OPLL) followed by internal carotid artery injury (n = 5) in sellar and parasellar pathologies. One patient developed basilar artery injury during endoscopic third ventriculostomy (ETV). Eight patients had pseudoaneurysm and seven had dissecting aneurysm with or without complete thrombosis of the involved artery. A total of two patients died after vascular injury and remaining thirteen patients survived and discharged. Conclusions: The adage "prevention is better than cure" applies most aptly in such cases. Any major vessel injury should be followed by immediate angiography and subsequent early management. The endovascular management is more favorable as these aneurysms are difficult to clip due to the absence of a neck and fragile wall.

Balancing the Extent of Resection and Ischemic Complications in Insular Glioma Surgery: Technical Nuances and Proposal of a Novel Composite Postoperative Outcome Index.

Background: Maximal safe resection remains the most desired goal of insular glioma surgery. Intraoperative surgical adjuncts provide better tumor visualization and real-time "safety" data but remain limited due to a high cost and limited availability. Objective: To highlight the importance of anatomical landmarks in insular glioma resection and avoidance of vascular complications. We also propose to objectify the onco-functional balance in insular glioma surgery. Methods: Forty-six insular gliomas operated upon by a single surgeon between January 2015 and February 2020 were reviewed, focusing on the operative technique and clinical outcomes. A novel composite postoperative outcome index (CPOI) was designed, comprising the extent of resection and permanent postoperative deficits, and utilized to assess the surgical outcomes. Results: Gross-total, near-total, and subtotal resections were achieved in 10.9%, 52.1% (n = 24), and 36.9% (n = 17) patients, respectively. The median overall survival (OS) was 20 months (95% CI = 9.56-30.43). CPOI was optimal in 38 patients (82.6%). A well-defined tumor margin (P = 0.01) and surgeon's experience (P = 0.04) were significantly associated with an optimal CPOI. Out of seven (15.2%) patients who developed permanent neurological deficits, three (6.5%) patients had severe disability. Favorable prognostic factors of survival included younger age (<40 years) (P = 0.002), tumors with only frontal lobe extension (P = 0.011), tumors with caudate head involvement (P = 0.04), and non-glioblastoma histology (P = 0.006). Conclusion: Tumor margin and increasing surgeon experience are critical to an optimal postoperative outcome. Respecting the basi-sulcal plane is key to lenticulostriate artery preservation. Caudate head involvement is a new favorable prognostic factor in insular gliomas.

Thirteen-and-a-half Syndrome Secondary to the Brainstem Cavernoma.

Background: "Thirteen-and-a-half" is a newly described clinical syndrome characterized by the combination of the one-and-a-half syndrome with fifth and seventh cranial nerve nuclei involvement (11/2 + 5 + 7 = 131/2). To the authors' knowledge, this is the first report of the thirteen-and-a-half syndrome secondary to pontine cavernoma and, overall, only the second reported case of this syndrome in the literature till date. Case Report: A 20-year-old man presented with the clinical features suggestive of the thirteen-and-a-half syndrome, explained radiologically by pontine cavernoma. We operated him using a suboccipital transvermian approach and he is doing well at 2.5 years follow-up. Interestingly, his one-and-a-half syndrome has partially improved to left horizontal gaze palsy. Conclusion: The clinical appreciation of the thirteen-and-a-half syndrome precisely localizes the lesion to ipsilateral dorsal pontine tegmentum. Neurosurgeons must be aware of the newly described "one-and-a-half- plus" syndromes as they help in a better understanding of pathoanatomy caused by different disease processes in the brainstem.

Examining the benefits of extended reality in neurosurgery: A systematic review.

While well-established in other surgical subspecialties, the benefits of extended reality, consisting of virtual reality (VR), augmented reality (AR), and mixed reality (MR) technologies, remains underexplored in neurosurgery despite its increasing utilization. To address this gap, we conducted a systematic review of the effects of extended reality (XR) in neurosurgery with an emphasis on the perioperative period, to provide a guide for future clinical optimization. Seven primary electronic databases were screened following guidelines outlined by PRISMA and the Institute of Medicine. Reported data related to outcomes in the perioperative period and resident training were all examined, and a focused analysis of studies reporting controlled, clinical outcomes was completed. After removal of duplicates, 2548 studies were screened with 116 studies reporting measurable effects of XR in neurosurgery. The majority (82%) included cranial based applications related to tumor surgery with 34% showing improved resection rates and functional outcomes. A rise in high-quality studies was identified from 2017 to 2020 compared to all previous years (p = 0.004). Primary users of the technology were: 56% neurosurgeon (n = 65), 28% residents (n = 33) and 5% patients (n = 6). A final synthesis was conducted on 10 controlled studies reporting patient outcomes. XR technologies have demonstrated benefits in preoperative planning and multimodal neuronavigation especially for tumor surgery. However, few studies have reported patient outcomes in a controlled design demonstrating a need for higher quality data. XR platforms offer several advantages to improve patient outcomes and specifically, the patient experience for neurosurgery.

Technical aspects and operative nuances using a high-definition 4K-3-dimensional exoscope for carotid endarterectomy surgery.

PURPOSE: Carotid endarterectomy (CEA) is effective in treating carotid artery stenosis to prevent stroke. Historically, this operation has been performed utilizing loupe magnification with or without the operating microscope (OM). However, there remains a need for continued improvement in operative visualization and surgical ergonomics. Recently, newly developed digital 'exoscope' has provided the surgeon with unique lighting and magnification as well as improvements in surgical ergonomics and working angle. We sought to review our cumulative experience using a novel 4K high-definition (4K-HD) 3-dimensional (3D) exoscope (EX) for CEA surgery. METHODS: All CEA surgery cases at our institution between 2013 and 2019 using the 4K-HD 3D EX were reviewed. Operative parameters, patient outcome and operator's assessment of the EX compared to OM-assisted cases was conducted. RESULTS: 28 patients were treated, 10 of which were operated using the EX. All procedures were performed without perioperative complications, or significant differences in operative parameters (blood loss <20 cm3 and 164 ± 49.5 minutes) compared to OM-assisted cases. Operators reported improved level of comfort performing 'high' bifurcation surgery and improved visualization and posture during inspection of the distal ICA lumen as primary advantages of EX-assisted CEA over OM-assisted CEA. CONCLUSIONS: The ORBEYE EX, albeit a learning curve necessitating a short period of the OR team, provided safety and outcome comparable to OM-assisted surgery. Potential advantages noted were improved visualization and ergonomics specifically for when extreme working angles were required. Our experience suggests that the exoscope may become a valuable alternative to standard magnification tools in CEA surgery.

The Dilemma of Multifocality in Insular Tumors: Multicentricity versus Metastasis.

BACKGROUND AND PURPOSE: Multifocality and metastasis from insular glioma are extremely rare. Pathological insights and elaboration of the clinical course of this condition will contribute to their better understanding. MATERIALS AND METHODS: Among 123 consecutively operated insular gliomas, 5 patients (4.2%) presented with a multifocal tumor. The clinico-radiological, histo-molecular, and treatment outcomes were noted and compared with the unifocal insular glioma cohort. RESULTS: Among the five patients, all were males and involved the right insular lobe. Three patients presented with synchronous tumors, while two patients developed metachronous multifocal tumors. The histology of the insular tumor was Grade I glioma in 1, Grade II astrocytoma with p53 mutation in 2, and anaplastic astrocytoma and glioblastoma in one patient each. Histological confirmation of the second lesion was performed in two patients, showing the same histology of the insular tumor. Interconnection between the tumors was apparent through cerebrospinal fluid pathways in four patients, while no such connection could be established in one patient. Barring the patient of Grade I glioma, the rest of the patients died within months of the diagnosis. CONCLUSION: Multifocal insular glioma is rare and probably represents a biologically more aggressive tumor. Insular glioma that touches the ventricle appears a common denominator for multifocality. True multicentricity is rare. The prognosis in insular glioma with multifocality is poor in non-Grade I gliomas.

5-Aminolevulinic Acid-Shedding Light on Where to Focus.

BACKGROUND: Surgical management of gliomas is predicated on "safe maximal resection" across all histopathologic grades because progression-free survival and overall survival are positively affected by the increasing extent of resection. Administration of the prodrug 5-aminolevulinic acid (5-ALA) induces tumor fluorescence with high specificity and sensitivity for malignant high-grade glioma (HGG). Fluorescence-guided surgery (FGS) using 5-ALA improves the extent of resection in the contrast-enhancing and nonenhancing tumor components in HGG. It has also shown preliminary usefulness in other central nervous system tumors, but with certain limitations. METHODS: We review and discuss the state of 5-ALA FGS for central nervous system tumors and identify the limitations in its use as a guide for future clinical optimization. RESULTS: 5-ALA FGS provides maximum clinical benefits in the treatment of newly diagnosed glioblastoma. 5-ALA fluorescence specificity is limited in low-grade glioma, recurrent HGG, and non-glial tumors. Several promising intraoperative adjuncts to 5-ALA FGS have been developed to expand its indications and improve the clinical efficacy and usefulness of 5-ALA FGS. CONCLUSIONS: 5-ALA FGS improves the clinical outcomes in HGG. However, further optimization of the diagnostic performance and clinical use of 5-ALA FGS is necessary for low-grade glioma and recurrent HGG tumors. Neurosurgical oncology will benefit from the novel use of advanced technologies and intraoperative visualization techniques outlined in this review, such as machine learning, hand-held fibe-optic probes, augmented reality, and three-dimensional exoscope assistance, to optimize the clinical usefulness and operative outcomes of 5-ALA FGS.

Surgery in High-Grade Insular Tumors: Oncological and Seizure Outcomes from 41 Consecutive Patients.

BACKGROUND: Insular high-grade gliomas are uncommon and constitute approximately 10% of all intracranial high-grade gliomas. Several publications in the recent years have thrown substantial light in the understanding of insular low-grade gliomas. However, there is a paucity of information concerning the spectrum of high-grade lesions affecting the insula, the mode of presentation vis-à-vis low-grade gliomas, and the survival rates to modern therapy. AIMS AND OBJECTIVES: We aim to highlight various clinical patterns, histo-pathological spectrum and the survival rates in patients with high-grade insular lesions. Also, we explore the factors that govern favourable outcomes. MATERIALS AND METHODS: A retrospective study of 41 patients operated for high-grade insular tumors at our institute between March 2010 to December 2018 was done to evaluate the clinico-radiological features, surgical nuances, survival rates and seizure outcomes. RESULTS: Raised intracranial pressure was the most frequent clinical presentation (n=28/41, 68.3%). Nearly 60% of the patients (n=25) had involvement of all four Berger-Sanai zones. The high-grade tumors encountered in our series were: glioblastoma (n=15), gliosarcoma (n=3), and embryonal tumor, not otherwise specified in 3 patients, while 21 patients had grade 3 astrocytoma. 33 out of 41 patients (80.5%) in our study showed excellent seizure control (ILAE grade 1A) at follow-up. Clinical presentation with seizures (P = 0.01, HR=0.3), WHO grade IV histopathology (P = 0.04, HR=3.7) and development of recurrence (P = 0.05, HR=5.5) were found to be independent predictors of OS. CONCLUSION: Insular high-grade gliomas are commoner than thought and nearly half of these are grade IV tumors (51%). A presentation with seizures may indicate precursor low-grade gliomas and portend a better survival. A maximum "safe" surgical resection, keeping the postoperative quality of life in mind, should be the goal.

Updates on Deep Learning and Glioma: Use of Convolutional Neural Networks to Image Glioma Heterogeneity.

Deep learning represents end-to-end machine learning in which feature selection from images and classification happen concurrently. This articles provides updates on how deep learning is being applied to the study of glioma and its genetic heterogeneity. Deep learning algorithms can detect patterns in routine and advanced MR imaging that elude the eyes of neuroradiologists and make predictions about glioma genetics, which impact diagnosis, treatment response, patient management, and long-term survival. The success of these deep learning initiatives may enhance the performance of neuroradiologists and add greater value to patient care by expediting treatment.

Vascularized Temporoparietal Fascial Flap: A Novel Surgical Technique to Bypass the Blood-Brain Barrier in Glioblastoma.

BACKGROUND: The major difficulty in treating glioblastoma stems from the intrinsic privileged nature of the brain. This complicates therapy, as many traditionally potent chemotherapeutics cannot access their target sites in the brain. Several techniques have been investigated to overcome this barrier and facilitate drug delivery. However, these techniques have inherent shortcomings related to the delivery system, the drug itself, or its bioactivity. Periosteal flaps and temporoparietal fascial flaps (TPFFs) are widely used options because they have predictable vasculature and a wide rotational arc. These flaps are not restricted by the blood-brain barrier, as they derive their vascular supply from branches of the external carotid artery, which can be readily identified with Doppler ultrasound. We hypothesized that transposition of a vascularized TPFF to the walls of a resected tumor surgical cavity may bring autologous tissue not restricted by the blood-brain barrier in close vicinity of the resected tumor bed microenvironment. This offers a nonselective, long-lasting gateway to target the residual tumor cells nesting in the brain adjacent to the tumor. CASE DESCRIPTION: A 47-year-old, right-handed woman with newly diagnosed multifocal glioblastoma underwent excision of the tumor and TPFF placement. This illustrative case report represents the first case of the use of this novel surgical technique with radiologic follow-up. CONCLUSIONS: The blood-brain barrier is identified as a major barrier for effective drug delivery in glioblastoma. This study demonstrates the feasibility of the TPFF technique to bypass this barrier and help facilitate the goal of improving drug delivery.