Clinical relevance of intracranial hemorrhage after thrombectomy versus medical management for large core infarct: a secondary analysis of the SELECT2 randomized trial.

BACKGROUND: The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized. METHODS: SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined. RESULTS: Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3-6) vs 4 (3-6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (Pinteraction=0.77). CONCLUSIONS: ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

Comparison of Radial Versus Femoral Access for Neuroendovascular Procedures in Very High Body Mass Index Individuals.

BACKGROUND: Femoral access (TFA) for neuroendovascular procedures may present a challenge in very high body mass index (BMI) individuals. Whether radial access (TRA) confers a comparative benefit in this specific population has not been studied. METHODS: We retrospectively identified all patients undergoing neuroendovascular procedures at our center between 2017 and 2021 with BMI ≥35 kg/m2. A total of 335 patients met our inclusion criteria, with 224 undergoing femoral access and 111 undergoing radial access. Electronic medical records were reviewed for baseline clinical and angiographic characteristics and procedural outcomes. RESULTS: The primary outcome of any bleeding complication occurred in 7% of the femoral group and 2% of the radial group (odds ratio 4.2, 95% confidence interval 1.0-18.6, P = 0.0421). Radial access was also associated with significantly shorter mean procedure times (median 43 minutes for radial, median 58 minutes for femoral, P = 0.0009) and mean fluoroscopy exposure times (median 15 minutes for radial, median 20 minutes for femoral, P = 0.0003). There were no significant differences in nonaccess site complications, procedural failure, length of stay, or deaths during hospitalization. CONCLUSIONS: When compared to TRA, TFA was associated with a significantly greater rate of bleeding complications in very high BMI patients undergoing neuroendovascular procedures. Procedure time and fluoroscopy time were both significantly longer when using TFA compared to TRA in this patient population.

The Evolving Role of Postgraduate Year 7 in Neurological Surgery Residency.

BACKGROUND AND OBJECTIVES: In 2013, all neurosurgery programs were mandated to adopt a 7-year structure. We sought to characterize how programs use the seventh year of training (postgraduate year 7 [PGY7]). METHODS: We surveyed all accredited neurosurgery programs in the United States regarding the PGY7 residents' primary role and the availability of enfolded fellowships. We compiled responses from different individuals in each program: chair, program director, program coordinator, and current chiefs. RESULTS: Of 120 accredited neurological surgery residency programs within the United States, 91 (76%) submitted responses. At these programs, the primary roles of the PGY7 were chief of service (COS, 71%), enfolded fellowships (EFF, 18%), transition to practice (10%), and elective time (1%). Most residencies have been 7-year programs for >10 years (52, 57%). Sixty-seven programs stated that they offer some form of EFF (73.6%). The most common EFFs were endovascular (57, 62.6%), spine (49, 53.9%), critical care (41, 45.1%), and functional (37, 40.7%). These were also the most common specialties listed as Committee on Advanced Subspecialty Training accredited by survey respondents. Spine and endovascular EFFs were most likely to be restricted to PGY7 (24.2% and 23.1%, respectively), followed by neuro-oncology (12, 13.2%). The most common EFFs reported as Committee on Advanced Subspecialty Training accredited but not restricted to PGY7 were endovascular (24, 26.4%) and critical care (23, 25.3%). CONCLUSION: Most accredited neurological surgery training programs use the COS as the primary PGY7 role. Programs younger in their PGY7 structure seem to maintain the traditional COS role. Those more established seem to be experimenting with various roles the PGY7 year can fill, including enfolded fellowships and transition-to-practice years, predominantly. Most programs offer some form of enfolded fellowship. This serves as a basis for characterization of how neurological surgery training may develop in years to come.

Surgical Strategies in the Treatment of Giant Pituitary Adenomas.

BACKGROUND AND OBJECTIVES: The management of giant pituitary adenomas (GPAs) is challenging due to associated endocrinopathies and the close proximity of these tumors to critical structures, such as the optic nerves, structures of the cavernous sinus, and hypothalamus. The objective of this review article was to summarize the current management strategies for giant pituitary adenomas, including the role of open and endoscopic surgical approaches and the role of medical and radiation therapy in conjunction with surgery. METHODS: We conducted a retrospective review of GPAs operated at our institute between January 2010 and March 2023. Surgical approaches, extent of resection, and associated complications were documented. Furthermore, we conducted a thorough literature review to identify relevant studies published in the past decade, which were incorporated along with insights gained from our institutional case series of GPAs to analyze and integrate both the existing knowledge base and our institution's firsthand experience in the management of GPAs. RESULTS: A total of 46 giant pituitary adenomas (GPAs) were operated on, using various surgical approaches. Transsphenoidal approach was used in 25 cases and a staged approach using transsphenoidal and pterional was used in 15 cases. Other approaches included transcortical-transventricular, transcallosal, pterional/orbitozygomatic, and subfrontal approaches. Complications and technical nuances were reported. CONCLUSION: The management of giant pituitary adenomas remains complex, often involving several modalities-open or endoscopic resection, radiosurgery, and medical management of both the tumor and associated endocrinopathies. Surgical resections are often challenging procedures that require careful consideration of several factors, including patient characteristics, tumor location, and size, and the experience and skill of the surgical team.

Feasibility of robotic neuroendovascular surgery.

BACKGROUND: Several recent reports of CorPath GRX vascular robot (Cordinus Vascular Robotics, Natick, MA) use intracranially suggest feasibility of neuroendovascular application. Further use and development is likely. During this progression it is important to understand endovascular robot feasibility principles established in cardiac and peripheral vascular literature which enabled extension intracranially. Identification and discussion of robotic proof of concept principals from sister disciplines may help guide safe and accountable neuroendovascular application. OBJECTIVE: Summarize endovascular robotic feasibility principals established in cardiac and peripheral vascular literature relevant to neuroendovascular application. METHODS: Searches of PubMed, Scopus and Google Scholar were conducted under PRISMA guidelines1 using MeSH search terms. Abstracts were uploaded to Covidence citation review (Covidence, Melbourne, AUS) using RIS format. Pertinent articles underwent full text review and findings are presented in narrative and tabular format. RESULTS: Search terms generated 1642 articles; 177, 265 and 1200 results for PubMed, Scopus and Google Scholar respectively. With duplicates removed, title review identified 176 abstracts. 55 articles were included, 45 from primary review and 10 identified during literature review. As it pertained to endovascular robotic feasibility proof of concept 12 cardiac, 3 peripheral vascular and 5 neuroendovascular studies were identified. CONCLUSIONS: Cardiac and peripheral vascular literature established endovascular robot feasibility and efficacy with equivalent to superior outcomes after short learning curves while reducing radiation exposure >95% for the primary operator. Limitations of cost, lack of haptic integration and coaxial system control continue, but as it stands neuroendovascular robotic implementation is worth continued investigation.

Scientific Influence of R01 Grants Issued to Department of Surgery Investigators, 2000 to 2015.

This observational study uses citation rates to measure the influence of National Institutes of Health R01 grants issued to department of surgery investigators and compared them according to whether the investigator was a surgeon-scientist or a research-scientist.

Multimodal monitoring to guide neurosurgical intervention in high-grade aneurysmal subarachnoid hemorrhage: illustrative case.

BACKGROUND: Multimodal monitoring to guide medical intervention in high-grade aneurysmal subarachnoid hemorrhage (aSAH) is well described. Multimodal monitoring to guide surgical intervention in high-grade aSAH has been less studied. OBSERVATIONS: Intracranial pressure (ICP), brain lactate to pyruvate ratio (L/P ratio), and brain parenchymal oxygen tension (pO2) were used as surrogates for clinical status in a comatose man after high-grade aSAH. Acute changes in ICP, L/P ratio, and pO2 were used to identify brain injury from both malignant cerebral edema and delayed cerebral ischemia, respectively, and decompressive hemicraniectomy with clot evacuation and intraarterial nimodipine were used to treat these conditions. The patient showed marked improvement in multimodal parameters following each intervention and eventually recovered to a modified Rankin score of 2. LESSONS: In patients with a limited neurological examination due to severe acute brain injury in the setting of aSAH, multimodal monitoring can be used to guide surgical treatment. With prompt, aggressive, maximal medical and surgical interventions, otherwise healthy individuals may retain the capacity for close to full recovery from seemingly catastrophic aSAH.

The 25 most cited articles on lateral lumbar interbody fusion: short review.

The lateral lumbar interbody fusion technique for lumbar arthrodesis is gaining popularity and being added as an option to traditional posterior and anterior approaches. In light of this, we analyzed the literature to identify the 25 most cited articles regarding lateral lumbar interbody fusion. The Thomson Reuters Web of Science was systematically searched to identify papers pertaining to lateral lumbar interbody fusion. The results were sorted in order to identify the top cited 25 articles. Statistical analysis was applied to determine metrics of interest, and observational studies were further classified. A search of all databases in the Thomson Reuters Web of Science identified 379 articles pertaining to lateral lumbar interbody fusion, with a total of 3800 citations. Of the 25 most cited articles, all were case series, reporting on a total of 2981 patients. These 25 articles were cited 2232 times in the literature and total citations per article ranged from 29 to 433. The oldest article was published in 2006, whereas the most recent article was published in 2015. The most cited article, by Ozgar et al., was cited 433 times, and the journal Spine published 7 of the 25 most cited articles. Herein, we report and analyze the 25 most cited articles on lateral lumbar interbody fusion, which include 25 cases series reporting a variety of data on a total of 2513 patients. Such data might assist in the design and interpretation of future studies pertaining to this topic.

Comparison of Lumbar Laminectomy Alone, Lumbar Laminectomy and Fusion, Stand-alone Anterior Lumbar Interbody Fusion, and Stand-alone Lateral Lumbar Interbody Fusion for Treatment of Lumbar Spinal Stenosis: A Review of the Literature.

Lumbar spinal stenosis is defined as narrowing of the lumbar spinal canal, which causes compression of the spinal cord and nerves. Spinal stenosis can cause leg pain and potentially back pain that can affect the quality of life. Ultimately, surgical decompression is required to alleviate the symptoms. In this review, we first utilize several important studies to compare lumbar laminectomy alone versus lumbar laminectomy and fusion. We also compare the effectiveness of more novel surgical approaches, stand-alone anterior lumbar interbody fusion (ALIF), and stand-alone lateral lumbar interbody fusion (LLIF). These techniques have their own advantages and disadvantages in which many factors must be taken into account before choosing a surgical approach. In addition, the patient's anatomy and pathology, lifestyle, and desires should be analyzed to help determine the ideal surgical strategy.

The endocannabinoid system and stroke: A focused review.

Stroke is an important cause of morbidity and mortality worldwide. Development of novel neuroprotectants is of paramount importance. This review seeks to summarize the recent evidence for the role of the endocannabinoid signaling system in stroke pathophysiology, as well as the evidence from preclinical studies regarding the efficacy of cannabinoids as neuroprotective therapies in the treatment of stroke. Recent evidence from rodent models implicating cannabinoid 1 receptor (CB1R), cannabinoid 2 receptor (CB2R), and CB1R and CB2R co-antagonism as neuroprotective strategies in stroke are reviewed. Rodent evidence for the therapeutic role of the endocannabinoid system in treating poststroke depression is reviewed. Finally, evidence for the role of cannabidiol, a publicly available cannabinoid that does not bind directly to known endocannabinoid receptors, as a stroke neuroprotectant is also reviewed. The review closes with a consideration of the role of human cannabinoid abuse in stroke and considers future directions for research on endocannabinoid-based stroke therapeutics.

Effect of revascularization on cognitive outcomes in intracranial steno-occlusive disease: a systematic review.

OBJECTIVESteno-occlusive diseases of the cerebral vasculature have been associated with cognitive decline. The authors performed a systematic review of the existing literature on intracranial steno-occlusive disease, including intracranial atherosclerosis and moyamoya disease (MMD), to determine the extent and quality of evidence for the effect of revascularization on cognitive performance.METHODSA systematic search of PubMed/MEDLINE, the Thomson Reuters Web of Science Core Collection, and the KCI Korean Journal Database was performed to identify randomized controlled trials (RCTs) in the English-language literature and observational studies that compared cognitive outcomes before and after revascularization in patients with steno-occlusive disease of the intracranial vasculature, from which data were extracted and analyzed.RESULTSNine papers were included, consisting of 2 RCTs and 7 observational cohort studies. Results from 2 randomized trials including 142 patients with symptomatic intracranial atherosclerotic steno-occlusion found no additional benefit to revascularization when added to maximal medical therapy. The certainty in the results of these trials was limited by concerns for bias and indirectness. Results from 7 observational trials including 282 patients found some cognitive benefit for revascularization for symptomatic atherosclerotic steno-occlusion and for steno-occlusion related to MMD in children. The certainty of these conclusions was low to very low, due to both inherent limitations in observational studies for inferring causality and concerns for added risk of bias and indirectness in some studies.CONCLUSIONSThe effects of revascularization on cognitive performance in intracranial steno-occlusive disease remain uncertain due to limitations in existing studies. More well-designed randomized trials and observational studies are needed to determine if revascularization can arrest or reverse cognitive decline in these patients.

Rosiglitazone augments antioxidant response in the human trophoblast and prevents apoptosis†.

Insufficient perfusion of the trophoblast by maternal blood is associated with an increased generation of reactive oxygen species and complications of the placenta. In this study, we first examined whether rosiglitazone, an agonist of the peroxisome proliferator-activated receptor-γ (PPARγ), protects the human trophoblast from oxidative injury by regulating key antioxidant proteins, catalase (CAT) and the superoxide dismutases (SOD1 and SOD2). In first trimester placental explants, localization of CAT was limited to cytotrophoblasts, whereas SOD1 was expressed in both the cyto- and syncytiotrophoblasts. In first trimester placental explants, hypoxia decreased the expression of both SOD1 and SOD2, and increased apoptosis. Treatment with rosiglitazone dose-dependently upregulated anti-oxidative CAT and SOD2, and rescued hypoxic injury in first trimester villous explants and JEG-3 cells, strongly suggesting the involvement of the PPARγ in regulating their expressions. Rosiglitazone facilitated transcription activity of PPARγ, and enhanced promotor binding, increased transcriptional activity at the CAT promoter, and elevated protein expression/activity. Treatment of hypoxic JEG-3 cells with rosiglitazone resulted in mitochondrial membrane potential increase and a reduction of caspase 9 and caspase 3 activity which is consistent with improved cell survival. To complement PPARγ activation data, we also utilized the antagonist (SR-202) and siRNA to suppress PPARγ expression and demonstrate the specific role of PPARγ in reducing ROS and oxidative stress. Ex vivo examination of term human placenta revealed lower expression of antioxidant proteins in pathologic compared to healthy placental tissues, which could be rescued by rosiglitazone, indicating that rosiglitazone can improve survival of the trophoblast under pathological conditions. These findings provide evidence that the PPARγ pathway directly influences cellular antioxidants production and the pathophysiology of placental oxidative stress.

Transposon mediated integration of plasmid DNA into the subventricular zone of neonatal mice to generate novel models of glioblastoma.

An urgent need exists to test the contribution of new genes to the pathogenesis and progression of human glioblastomas (GBM), the most common primary brain tumor in adults with dismal prognosis. New potential therapies are rapidly emerging from the bench and require systematic testing in experimental models which closely reproduce the salient features of the human disease. Herein we describe in detail a method to induce new models of GBM with transposon-mediated integration of plasmid DNA into cells of the subventricular zone of neonatal mice. We present a simple way to clone new transposons amenable for genomic integration using the Sleeping Beauty transposon system and illustrate how to monitor plasmid uptake and disease progression using bioluminescence, histology and immuno-histochemistry. We also describe a method to create new primary GBM cell lines. Ideally, this report will allow further dissemination of the Sleeping Beauty transposon system among brain tumor researchers, leading to an in depth understanding of GBM pathogenesis and progression and to the timely design and testing of effective therapies for patients.