Mesenchymal stem cell therapy for focal epilepsy: A systematic review of preclinical models and clinical studies.

Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: (("mesenchymal") AND ("stem cell")) AND (("epilepsy") OR ("convulsion") OR ("seizures")). This review followed Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ-aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.

The early infiltrative phase of GBM hypothesis: are molecular glioblastomas histological glioblastomas in the making? A preliminary multicenter study.

PURPOSE: The presence of necrosis or microvascular proliferation was previously the hallmark for glioblastoma (GBM) diagnosis. The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/-10 copy changes. We hypothesize that these tumors are early histological GBM and will eventually develop the classic histological features. METHODS: Medical records from 65 consecutive patients diagnosed with molGBM at three tertiary-care centers from our institution were retrospectively reviewed from November 2017-October 2021. Only patients who underwent reoperation for tumor recurrence and whose tissue at initial diagnosis and recurrence was available were included in this study. The detailed clinical, histopathological, and radiographic scenarios are presented. RESULTS: Five patients were included in our final cohort. Three (60%) patients underwent reoperation for recurrence in the primary site and 2 (40%) underwent reoperation for distal recurrence. Microvascular proliferation and pseudopalisading necrosis were absent at initial diagnosis but present at recurrence in 4 (80%) patients. Radiographically, all tumors showed contrast enhancement, however none of them showed the classic radiographic features of GBM at initial diagnosis. CONCLUSIONS: In this manuscript we present preliminary data for a hypothesis that molGBMs are early histological GBMs diagnosed early in their natural history of disease and will eventually develop necrosis and microvascular proliferation. Further correlative studies are needed in support of this hypothesis.

The survival outcomes of molecular glioblastoma IDH-wildtype: a multicenter study.

PURPOSE: Histological diagnosis of glioblastoma (GBM) was determined by the presence of necrosis or microvascular proliferation (histGBM). The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM, WHO grade 4) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/- 10 copy changes. The objective of this study was to explore and compare the survival outcomes between histGBM and molGBM. METHODS: Medical records for patients diagnosed with GBM at the three tertiary care academic centers of our institution from November 2017 to October 2021. Only patients who underwent adjuvant chemoradiation were included. Patients without molecular feature testing or with an IDH mutation were excluded. Univariable and multivariable analyses were performed to evaluate progression-free (PFS) and overall- survival (OS). RESULTS: 708 consecutive patients were included; 643 with histGBM and 65 with molGBM. Median PFS was 8 months (histGBM) and 13 months (molGBM) (p = 0.0237) and median OS was 21 months (histGBM) versus 26 months (molGBM) (p = 0.435). Multivariable analysis on the molGBM sub-group showed a worse PFS if there was contrast enhancement on MRI (HR 6.224 [CI 95% 2.187-17.714], p < 0.001) and a superior PFS on patients with MGMT methylation (HR 0.026 [CI 95% 0.065-0.655], p = 0.007). CONCLUSIONS: molGBM has a similar OS but significantly longer PFS when compared to histGBM. The presence of contrast enhancement and MGMT methylation seem to affect the clinical behavior of this subset of tumors.

Treatment of recurrent and persistent Cushing's disease after first transsphenoidal surgery: lessons learned from an international meta-analysis.

PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for patients with Cushing's Disease (CD). Recurrence rates after a first TSS range between 3 and 22% within 3 years. Management of recurrent or persistent CD may include repeat TSS or stereotactic radiosurgery (SRS). We performed a meta-analysis to explore the overall efficacy of TSS and SRS for patients with CD after an initial surgical intervention. METHODS: EMBASE, PubMed, SCOPUS, and Cochrane databases were searched from their dates-of-inception up to December 2021. Inclusion criteria were comprised of patients with an established diagnosis of CD who presented with persistent or biochemically recurrent disease after a first TSS for tumor resection and were treated with a second TSS or SRS. RESULTS: Search criteria yielded 2,116 studies of which 37 articles from 15 countries were included for analysis. Mean age ranged between 29.9 and 47.9 years, and mean follow-up was 11-104 months. TSS was used in 669 (67.7%) patients, while SRS was used in 320 (32.4%) patients, and remission rates for CD were 59% (95%CI 0.49-0.68) and 74% (95%CI 0.54-0.88), respectively. There was no statistically significant difference in the remission rate between TSS and SRS (P = 0.15). The remission rate of patients with recurrent CD undergoing TSS was 53% (95%CI 0.32-0.73), and for persistent CD was 41% (95%CI 0.28-0.56) (P = 0.36). CONCLUSION: Both TSS and SRS are possible approaches for the treatment of recurrent or persistent CD after a first TSS. Our data show that either TSS or SRS represent viable treatment options to achieve remission for this subset of patients.

Lumbar nerve root biopsy with fascicle dissection and functional mapping: how I do it.

BACKGROUND: Lumbosacral plexopathies with unclear etiology are a rare entity. In certain cases, if workup unrevealing and medical management is suboptimal, an open lumbar nerve root biopsy may be considered. METHOD: A standard lumbar laminectomy is performed for access to the intradural contents. The dura is opened at midline in a standard fashion. Single nerve roots are selected and stimulated for an EMG response. A nerve fascicle is then dissected and stimulated before excision. CONCLUSION: Lumbar nerve root biopsy is feasible and safe. All non-invasive workup needs to be completed and negative before performing this procedure.

Motor Cortex Stimulation for Pain: A Narrative Review of Indications, Techniques, and Outcomes.

BACKGROUND: Motor cortex stimulation (MCS) was introduced in 1985 and has been tested extensively for different types of peripheral and central neuropathic pain syndromes (eg, central poststroke pain, phantom limb pain, trigeminal neuropathic pain, migraines, etc). The motor cortex can be stimulated through different routes, including subdural, epidural, and transcranial. OBJECTIVES: In this review, we discuss the current uses, surgical techniques, localization techniques, stimulation parameters, and clinical outcomes of patients who underwent chronic MCS for treatment-resistant pain syndromes. MATERIALS AND METHODS: A broad literature search was conducted through PubMed to include all articles focusing on MCS for pain relief (keywords: subdural, epidural, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, motor cortex stimulation, pain). LITERATURE REVIEW: Epidural MCS was the most widely used technique and had varying response rates across studies. Long-term efficacy was limited, and pain relief tended to decrease over time. Subdural MCS using similar stimulation parameters demonstrated similar efficacy to epidural stimulation and less invasive methods, such as repetitive transcranial magnetic stimulation (rTMS), which have been shown to provide adequate pain relief. rTMS and certain medications (ketamine and morphine) have been shown to predict the long-term response to epidural MCS. Complications tend to be rare, the most reported being seizures during subdural or epidural stimulation or hardware infection. CONCLUSIONS: Scientific evidence supports the use of MCS for treatment of refractory neuropathic pain syndromes. Further studies are warranted to elucidate the specific indications and stimulation protocols that are most amenable to the different types of MCS.

Fluid Restriction After Transsphenoidal Surgery for the Prevention of Delayed Hyponatremia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Delayed hyponatremia is the primary cause of readmission after transsphenoidal surgery, with a reported incidence of 9% to 30.7%. Studies have failed to identify consistent predictive factors for postoperative hyponatremia; thus, it is difficult to determine patients that are at a high risk. Fluid restriction is one approach for the prevention of hyponatremia. We have performed a meta-analysis and systematic review of the literature to evaluate the impact of fluid restriction on hyponatremia and hospital readmissions. METHODS: Ovid EMBASE, PubMed, Scopus, and Cochrane were searched from inception to May 2021, using the Population, Intervention, Comparison, Outcome, and Study question format: Do patients who underwent transsphenoidal surgery and followed a postoperative fluid restriction regimen differ in terms of hyponatremia and readmission rates? Studies that implemented fluid restriction and reported hyponatremia and/or readmission rates were included for analysis. Data were pooled by meta-analysis and analyzed using fixed effect and random effect models. RESULTS: A total of 143 manuscripts representing 103 unique studies were identified, with 5 studies included for analysis, yielding a pooled cohort of 1586 patients: 594 on fluid restriction protocols and 992 control patients. Fluid restriction protocols ranged from 1.0 to 2.5 L and varied in the length time between postoperative days 1 to 15. Patients on fluid restriction had a decreased risk of hyponatremia (risk ratio: 0.34; 95% CI, 0.21-0.57; P < .00001) and readmission due to hyponatremia (risk ratio: 0.24; 95% CI, 0.09-0.63; P = .0038). CONCLUSION: Postoperative fluid restriction after transsphenoidal surgery represents an effective method for the prevention of hyponatremia and hospital readmission and has the potential to decrease health care costs.

Multiple meningiomas: does quantity matter? a population-based survival analysis with underlined age and sex differences.

INTRODUCTION: Intracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of small case series and individual reports. Hence, survival outcome data are limited. The Objective of this study is to explore the influence of sex, age, and number of lesions on overall survival (OS) in patients with MM. METHODS: We obtained demographic and clinical data from the surveillance, epidemiology, and end results program (SEER) on adult patients diagnosed with meningiomas from 1975 to 2017. Univariable and multivariable analyses were conducted to assess whether number of lesions, age, and sex had a significant influence on OS. RESULTS: 99,918 cases were included. Results showed that MM patients had a significantly decreased OS when compared to patients with a single lesion (median OS of 94 and 180 months, respectively; p < 0.001). Further analysis showed a progressive decrease on OS for every additional lesion; 2 (HR 1.659 [CI 95% 1.612-1.708], p < 0.001), 3 (HR 1.877 [CI 95% 1.773-1.988], p < 0.001), and ≥ 4 (HR 2.116 [CI 95% 1.886-2.373], p < 0.001). When assessing for sex differences, female patients had increased OS (HR 0.778 [CI 95% 0.743-0.815], p < 0.001) and decreased risk of developing MM (HR 0.809 [CI 95% 0.784-0.835], p < 0.001). CONCLUSION: Increasing number of meningiomas has a significant negative impact on OS, with a progressive decrease on survival for every additional lesion. Furthermore, female patients had increased OS and decreased risk to develop MM.

Cell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone.

Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially because of subventricular zone contact. Despite this, cross-talk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. In addition, GBM brain tumor-initiating cells (BTICs) increase expression of cathepsin B (CTSB) upon interaction with NPCs. Lentiviral knockdown and recombinant protein experiments reveal that both cell-intrinsic and soluble CTSB promote malignancy-associated phenotypes in BTICs. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Last, we show LV-proximal CTSB up-regulation in patients, showing the relevance of this cross-talk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM.

Radiographic Anatomy of the Common Carotid Artery for Direct Carotid Puncture.

BACKGROUND: Direct common carotid puncture (DCP) is conventionally used as a bailout technique in stroke patients. However, little is known about the relevant anatomy. Our objective was to examine the relationship of the common carotid artery (CCA) to surrounding structures based on different DCP trajectories passing through the artery's center. METHODS: Fifty randomly selected head/neck CTAs were analyzed. The trajectory of DCP and relationship to the internal jugular vein (IJV) and thyroid were analyzed at 1 cm intervals above the clavicle on 7 axial sections. Using the trans-carotid sagittal plane as the 0° trajectory, we plotted 3 additional trajectories at 30° intervals and the relationship with the IJV and thyroid proximity was graded as following: 0=absent, 1=adjacent, and 2=crossing. The CCA tortuosity index was also analyzed for each vessel. RESULTS: Analysis of 2800 trajectories across 100 CCAs showed that the IJV and thyroid were least encountered on the axial sections 2 cm above the clavicle, at 0° on the right (9 thyroids and 6 IJV), and at 90° on the left (0 Thyroids and 14 IJVs). The tortuosity index of the CCA was significantly lower above the clavicle than its entire length (P < 0.001). CONCLUSIONS: DCP performed 2 cm above the clavicle at 0° on the right, and 90° on the left appears to minimize encounters with the IJV and thyroid gland, reducing potential complications. However, despite these findings, ultrasound guidance remains vital for DCP safety. Further focus on endovascular device safety in DCP is needed.

Combined anterior and posterior circulation approach for stent-assisted coiling of a recurrent basilar tip aneurysm.

Endovascular treatment of recurrent basilar aneurysms is challenging due to significant changes in the configuration of the aneurysm and adjacent vessels from prior interventions.1 Coil compaction is a common cause of recurrence and alters the aneurysm morphology significantly.2-4 Stenting of the basilar artery into a posterior cerebral artery modifies the angles between these vessels.5 In this video, we discuss a combined approach via the anterior and posterior circulation for stent-assisted coiling of a recurrent basilar tip aneurysm (Video 1) . A patient in their 40s with a history of ruptured aneurysm underwent multiple endovascular interventions including coiling, stent-assisted coiling, and Woven Endobridge (WEB) device. The patient presented with worsening headaches and underwent treatment with stent-assisted coiling for recurrence. After encountering challenges with direct access from the basilar artery, a combined anterior and posterior circulation approach was used.6 The stent was deployed through the posterior communicating artery and a snare was used to navigate the complex anatomy. neurintsurg;15/5/512/V1F1V1Video 1 .

Bilateral Laser Interstitial Thermal Therapy for Butterfly Gliomas Compared With Needle Biopsy: A Preliminary Survival Study.

BACKGROUND AND OBJECTIVES: Bilateral/butterfly glioblastoma (bGBM) has a poor prognosis. Resection of these tumors is limited due to severe comorbidities that arise from surgical procedures. Laser interstitial thermal therapy (LITT) offers a minimally invasive cytoreductive therapy for deep-seated tumors such as bGBM. The objective of this study was to evaluate the safety of bilateral LITT in patients with bGBM. METHODS: Medical records of all consecutive patients diagnosed with bGBM by a single surgeon at a single institution from January 2014 to August 2022 were reviewed. Clinical, safety, and radiographic volumetric data were obtained. In addition, an exploratory analysis of survival was performed. RESULTS: A total of 25 patients were included; 14 underwent biopsy only, and 11 underwent biopsy + LITT (7 underwent bilateral and 4 underwent unilateral LITT). No (0%) intraoperative or postoperative complications were recorded in the treatment group. Tumor volume negatively correlated with extent of treatment (r 2 = 0.44, P = .027). The median progression-free survival was 2.8 months in the biopsy-only group and 5.5 months in the biopsy + LITT group ( P = .026). The median overall survival was 4.3 months in the biopsy-only group and 10.3 months in the biopsy + LITT group ( P = .035). CONCLUSION: Bilateral LITT for bGBM can be safely performed and shows early improvement of the progression-free survival and long-term survival outcomes of these patients.

Cell-specific crosstalk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone.

Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially due to subventricular zone (SVZ) contact. Despite this, crosstalk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. Additionally, GBM brain tumor initiating cells (BTICs) increase expression of CTSB upon interaction with NPCs. Lentiviral knockdown and recombinant protein experiments reveal both cell-intrinsic and soluble CTSB promote malignancy-associated phenotypes in BTICs. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Finally, we show LV-proximal CTSB upregulation in patients, showing the relevance of this crosstalk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM. Highlights: Periventricular GBM is more malignant and disrupts neurogenesis in a rodent model.Cell-specific proteomics elucidates tumor-promoting crosstalk between GBM and NPCs.NPCs induce upregulated CTSB expression in GBM, promoting tumor progression.GBM stalls neurogenesis and promotes NPC senescence via CTSB.

Phase 1, Dose Escalation, Nonrandomized, Open-Label, Clinical Trial Evaluating the Safety and Preliminary Efficacy of Allogenic Adipose-Derived Mesenchymal Stem Cells for Recurrent Glioblastoma: A Clinical Trial Protocol.

Background and Objectives: Despite standard of care with maximal safe resection and chemoradiation, glioblastoma is the most common and aggressive type of primary brain cancer. Surgical resection provides a window of opportunity to locally treat gliomas while the patient is recovering, and before initiating concomitant chemoradiation. To assess the safety and establish the maximum tolerated dose of adipose-derived mesenchymal stem cells (AMSCs) for the treatment of recurrent glioblastoma (GBM). Secondary objectives are to assess the toxicity profile and long-term survival outcomes of patients enrolled in the trial. Additionally, biospecimens will be collected to explore the local and systemic responses to this therapy. Methods: We will conduct a phase 1, dose escalated, non-randomized, open label, clinical trial of GBM patients who are undergoing surgical resection for recurrence. Up to 18 patients will receive intra-cavitary application of AMSCs encapsulated in fibrin glue during surgical resection. All patients will be followed for up to 5 years for safety and survival data. Adverse events will be recorded using the CTCAE V5.0. Expected Outcomes: This study will explore the maximum tolerated dose (MTD) of AMSCs along with the toxicity profile of this therapy in patients with recurrent GBM. Additionally, preliminary long-term survival and progression-free survival outcome analysis will be used to power further randomized studies. Lastly, CSF and blood will be obtained throughout the treatment period to investigate circulating molecular and inflammatory tumoral/stem cell markers and explore the mechanism of action of the therapeutic intervention. Discussion: This prospective translational study will determine the initial safety and toxicity profile of local delivery of AMSCs for recurrent GBM. It will also provide additional survival metrics for future randomized trials.

MIS lateral retroperitoneal transpsoas approach allows gross total resection of a giant L4 schwannoma.

In this surgical video, the authors present a successful minimally invasive (MIS) lateral retroperitoneal transpsoas approach for resection of an L4 nerve root schwannoma. They describe the surgical approach in detail, with special emphasis on patient positioning for an orthogonal view, as well as technical nuances throughout the procedure. Using a sequential tubular retractor, they performed a microscopic dissection of the lesion. The tumor was debulked and the tumor capsule was disconnected from the surrounding tissue. During dissection, direct stimulation identified a functional nerve root that was carefully dissected from the tumor capsule. The tumor was then removed en bloc. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID2220.

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

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

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

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

Influence of glucose levels on clinical outcome after mechanical thrombectomy for large-vessel occlusion: a systematic review and meta-analysis.

Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score <3 (risk ratio (RR): 0.65; 95% CI 0.59 to 0.72; p<0.0001; I 2=13%), and had an increased risk of symptomatic intracranial hemorrhage (sICH) (RR: 2.07; 95% CI 1.65 to 2.60; p<0.0001; I 2=0%) and mortality (RR: 1.73; 95% CI 1.57 to 1.91; p<0.0001; I 2=0%). Patients who present with hyperglycemia and undergo MT for treatment of LVO have an increased risk of unfavorable clinical outcome, sICH, and mortality. Glucose levels at admission appear to be a prognostic factor in this subset of patients. Further studies should focus on evaluating control of the glucose level at admission as a modifiable risk factor in patients undergoing MT for LVO.

Cerebral venous thrombosis during the COVID-19 Pandemic: A multi-center experience.

OBJECTIVE: To describe the clinical characteristics and outcomes of CVT in patients with history of recent COVID-19 infection or vaccination. METHODS: We reviewed demographic, clinical, and radiographic characteristics of non-pyrogenic, non-traumatic CVT cases at our multi-center institution between March 2020 and December 2021. Patients were grouped according to their history of recent COVID-19 infection or vaccination into group-I (+COVID-19 association) and group-II (-COVID-19 association). RESULTS: Fifty-one patients with CVT were included, of which 14 (27.4%) had a positive COVID-19 association: 10 with infection and 4 with mRNA-COVID-vaccine. Nine patients in group-I had COVID-19 infection or vaccine within 30 days of CVT diagnosis, including 3 patients with active infection at the time of CVT diagnosis. Half of the patients in group-I (n = 7,50.0%) and 32.4% (n = 12) of group-II were male, and mean age was 52.6 years in group-I and 51.4 years in group-II. Fever at presentation was noted in one patient who had active COVID infection (I=1 (7.1%), II= 0 (0%)). Higher rates of comorbidities were observed in group-II: hypertension (I= 2 (14.3%), II= 13 (35.1%)), deep venous thrombosis(I=1(7.1%), II= 10 (27.0%)), pulmonary emboli (I=1(7.1%), II= 8(21.6%)), or stroke(I=0(0%), II= 6(16.4%)). Three patients had thrombocytopenia at the time of CVT diagnosis (5.4%) and most patients (n = 37, 72.5%) were treated medically with anticoagulation. Complication rate during hospitalization was 17.6% (n = 6), and no mortality was noted. CONCLUSION: Twenty-seven percent of CVT patients were associated with COVID-19 infection or vaccination, and the majority presented within 30 days of infection/vaccination.

Influence of Platelet Count on Procedure-Related Outcomes After Mechanical Thrombectomy for Large Vessel Occlusion: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare outcomes between patients who underwent mechanical thrombectomy for large vessel occlusion based on platelet count: low versus normal. METHODS: Three studies were included with a pooled cohort of 1125 patients. Data points were collected and pooled by meta-analysis of proportions via a logit transformation to provide a summary statistic. Both fixed-effect and random-effects models were recruited for the analysis. In this meta-analysis, risk of developing symptomatic intracranial hemorrhage, unfavorable clinical outcomes (modified Rankin Scale score >3), and mortality of patients with low platelet counts were compared with patients with normal platelet counts according to the criteria for inclusion used by each study. RESULTS: Of patients, 50 (4.7%) had low platelet count, and 1075 (95.3%) had normal platelet count. Patients in the low platelet count group had a substantially higher risk of mortality (risk ratio 1.93, 95% confidence interval 1.43-2.60, P < 0.0001, I2 = 0%), but no differences in clinical outcomes (risk ratio 0.66, 95% confidence interval 0.40-1.11, P = 0.12, I2 = 0%) or symptomatic intracranial hemorrhage (risk ratio 2.03, 95% confidence interval 0.87-4.70, P = 0.10, I2 = 15%) were noted. CONCLUSIONS: Patients with low platelet counts had increased mortality compared with patients with normal platelet counts following mechanical thrombectomy for large vessel occlusion.