Bailout endovascular techniques applied in a complicated basilar thrombectomy case.

Patients with stroke symptoms due to acute basilar artery occlusion can benefit from endovascular thrombectomy.1 2 Several papers have reported unwanted events during thrombectomy procedures such as breakage, fragmentation, or even intravascular migration of the devices or catheter pieces. These papers also presented methods or techniques to retrieve defective devices such as a snare, retrievable stents, or balloons.3-6 Video 1 presents a case of basilar thrombectomy that was complicated with fragmentation and then distal migration of a Marksman microcatheter tip into the left posterior cerebral artery. The video shows the bailout technique that was used to retrieve the migrated catheter tip using a gentle/simple and posterior circulation-friendly technique-a technique based on fundamental neurointerventional concepts. neurintsurg;16/2/217/V1F1V1Video 1 This video demonstrates the use of a bailout technique to retrieve a migrated microcatehter tip after basilar artery thrombectomy.

Sonolucent Cranioplasty in Extracranial to Intracranial Bypass Surgery: Early Multicenter Experience of 44 Cases.

BACKGROUND: The new sonolucent cranioplasty implant (clear polymethyl methacrylate, PMMA) adds functionality besides surgical reconstruction. One possible application uses the transcranioplasty ultrasound (TCUS) technique after PMMA cranioplasty to assess graft patency of extracranial-intracranial (EC-IC) bypass procedures. OBJECTIVE: To report our early multicenter experience. METHODS: This is a multicenter analysis of consecutive EC-IC bypass patients from 5 US centers (2019-2022) with closure postbypass using PMMA implant. RESULTS: Forty-four patients (median age 53 years, 68.2% females) were included. The most common indication for bypass was Moyamoya disease/syndrome (77.3%), and superficial temporal artery to middle cerebral artery bypass was the most common procedure (79.5%). Pretreatment modified Rankin Scales of 0 and 1 to 2 were noted in 11.4% and 59.1% of patients, respectively. Intraoperative imaging for bypass patency involved a combination of modalities; Doppler was the most used modality (90.9%) followed by indocyanine green and catheter angiography (86.4% and 61.4%, respectively). Qualitative TCUS assessment of graft patency was feasible in all cases. Postoperative inpatient TCUS confirmation of bypass patency was recorded in 56.8% of the cases, and outpatient TCUS surveillance was recorded in 47.7%. There were no cases of bypass failure necessitating retreatment. Similarly, no implant-related complications were encountered in the cohort. Major complications requiring additional surgery occurred in 2 patients (4.6%) including epidural hematoma requiring evacuation (2.3%) and postoperative surgical site infection (2.3%) that was believed to be unrelated to the implant. CONCLUSION: This multicenter study supports safety and feasibility of using sonolucent PMMA implant in EC-IC bypass surgery with the goal of monitoring bypass patency using TCUS.

Principles, techniques and applications of high resolution cone beam CT angiography in the neuroangio suite.

The aim of this review is to describe the acquisition and reformatting of state of the art high resolution cone beam CT (HR-CBCT) and demonstrate its role in multiple neurovascular conditions as a tool to improve the understanding of disease and guide therapeutic decisions. First, we will review the basic principle of CBCT acquisition, followed by the injection protocols and the reformatting paradigms. Next, multiple applications in different pathological conditions such as aneurysms, arteriovenous malformations, dural arteriovenous fistulas, and stroke will be described. HR-CBCT angiography, widely available, is uniquely useful in certain clinical scenarios to improve the understanding of disease and guide therapeutic decisions. It rapidly is becoming an essential tool for the contemporary neurointerventionalist.AChoAho.

Cerebral venous anatomy: implications for the neurointerventionalist.

Meaningful contributions to neurointerventional practice may be possible by considering the dynamic aspects of angiography in addition to fixed morphologic information. The functional approach to venous anatomy requires integration of the traditional static anatomic features of the system-deep, superficial, posterior fossa, medullary veins, venous sinuses, and outflow routes into an overall appreciation of how a classic model of drainage is altered, embryologically, or pathologically, depending on patterns of flow-visualization made possible by angiography. In this review, emphasis is placed on balance between alternative venous networks and their redundancy, and the problems which arise when these systems are lacking. The role of veins in major neurovascular diseases, such as dural arteriovenous fistulae, arteriovenous malformations, pulsatile tinnitus, and intracranial hypertension, is highlighted, and deficiencies in knowledge emphasized.

Short- and long-term outcomes of moyamoya patients post-revascularization.

OBJECTIVE: The post-bypass stroke risk factors and long-term outcomes of moyamoya patients are not well documented. Therefore, the authors studied 30-day stroke risks and patients' long-term physical, functional, and social well-being. METHODS: This was a single-institution combined moyamoya disease (MMD) database interrogation and questionnaire study. From 1991 to 2014, 1250 revascularization procedures (1118 direct bypasses, 132 indirect bypasses) were performed in 769 patients. Completed questionnaires were received from and available for analysis on 391 patients, and 6-month follow-up data were available for 96.4% (741/769) of the patients. RESULTS: The patients consisted of 548 females and 221 males, with a mean age of 32 years (range 1-69 years). Three hundred fifty-eight bypasses were performed in 205 pediatric patients (73% direct bypasses), and 892 revascularizations were performed in 564 adults (96% direct bypasses). Fifty-two patients (6.8%) developed major strokes with a worsening modified Rankin Scale (mRS) score within 30 days postoperatively. The 30-day major stroke risk was 5.3% (41/769) and 2.6% (12/467) after the first and second bypasses, respectively. Logistic regression analysis revealed that older age, modified MRI (mMRI) score, and hemodynamic reserve (HDR) score are clearly associated with higher postoperative stroke risks. Over a mean follow-up of 7.3 years (range 0.5-26 years), the long-term stroke risk among 741 patients was 0.6% per patient-year; 75% of these patients had excellent outcomes (mRS score 0-1). The long-term outcome questionnaire study showed that 84% (234/277) of patients reported resolution or improvement in their preoperative headache, 83% (325/391) remained employed or in school, and 87% (303/348) were self-caring. CONCLUSIONS: In this large, single-center surgical series, most of the adult and pediatric patients had direct revascularization, with a 4.2% per-bypass-procedure (6.8% per patient) 30-day major stroke risk and a 0.6% per-patient-year long-term stroke risk. The authors identified various risk factors that are highly correlated with postoperative morbidity (age, mMRI score, and HDR score) and are involved in ongoing work to develop the predictive modeling for future patient selection and treatment.

How I do it: endarterectomy for carotid web.

BACKGROUND: The carotid web is an important and under recognized etiology for recurrent cryptogenic strokes. A management option for a symptomatic carotid web is a carotid endarterectomy (CEA) with surgical microdissection and removal of the intimal luminal defect. METHODS: We describe some of the technical nuances involved in successfully performing a carotid endarterectomy for resection of a carotid web. CONCLUSION: Utilizing a familiar approach to an understudied pathology, this procedure can be safely performed and provides the patient with lasting protection against recurrent infarcts through removal of the thromboembolic nidus.

Endarterectomy for symptomatic internal carotid artery web.

OBJECTIVE: The carotid web (CW) is an underrecognized source of cryptogenic, embolic stroke in patients younger than 55 years of age, with up to 37% of these patients found to have CW on angiography. Currently, there are little data detailing the best treatment practices to reduce the risk of recurrent stroke in these patients. The authors describe their institutional surgical experience with patients treated via carotid endarterectomy (CEA) for a symptomatic internal carotid artery web. METHODS: A retrospective, observational cohort study was performed including all patients presenting to the authors' institution with CW. All patients who were screened underwent either carotid artery stenting (CAS) or CEA after presentation with ischemic stroke from January 2019 to February 2020. From this sample, patients with suggestive radiological features and pathologically confirmed CW who underwent CEA were identified. Patient demographics, medical histories, radiological images, surgical results, and clinical outcomes were collected and described using descriptive statistics. RESULTS: A total of 45 patients with symptomatic carotid lesions were treated at the authors' institution during the time period. Twenty patients underwent CAS, 1 of them for a CW. Twenty-five patients were treated via CEA, and of these, 6 presented with ischemic strokes ipsilateral to CWs, including 3 patients who presented with recurrent strokes. The mean patient age was 55 ± 12.6 years and 5 of 6 were women. CT angiography or digital subtraction angiography demonstrated the presence of CWs ipsilateral to the stroke in all patients. All patients underwent resection of CWs using CEA. There were no permanent procedural complications and no patients had stroke recurrence following intervention at the latest follow-up (mean 6.1 ± 4 months). One patient developed mild tongue deviation most likely related to retraction, with complete recovery at follow-up. CONCLUSIONS: CEA is a safe and feasible treatment for symptomatic carotid webs and should be considered a viable alternative to CAS in this patient population.

Randomized Controlled Trials in Functional Neurosurgery-Association of Device Approval Status and Trial Quality.

INTRODUCTION: Randomized controlled trials (RCTs) have been critical in evaluating the safety and efficacy of functional neurosurgery interventions. Given this, we sought to systematically assess the quality of functional neurosurgery RCTs. METHODS: We used a database of neurosurgical RCTs (trials published from 1961 to 2016) to identify studies of functional neurosurgical procedures (N = 48). We extracted data on the design and quality of these RCTs and quantified the quality of trials using Jadad scores. We categorized RCTs based on the device approval status at the time of the trial and tested the association of device approval status with trial design and quality parameters. RESULTS: Of the 48 analyzed functional neurosurgery RCTs, the median trial size was 34.5 patients with a median age of 51. The most common indications were Parkinson's disease (N = 20), epilepsy (N = 10), obsessive-compulsive disorder (N = 4), and pain (N = 4). Most trials reported inclusion and exclusion criteria (95.8%), sample size per arm (97.9%), and baseline characteristics of the patients being studied (97.9%). However, reporting of allocation concealment (29.2%), randomization mode (66.7%), and power calculations (54.2%) were markedly less common. We observed that trial quality has improved over time (Spearman r, 0.49). We observed that trials studying devices with humanitarian device exemption (HDE) and experimental indications (EI) tended to be of higher quality than trials of FDA-approved devices (p = 0.011). A key distinguishing quality characteristic was the proportion of HDE and EI trials that were double-blinded, compared to trials of FDA-approved devices (HDE, 83.3%; EI, 69.2%; FDA-approved, 35.3%). Although more than one-third of functional neurosurgery RCTs reported funding from industry, no significant association was identified between funding source and trial quality or outcome. CONCLUSION: The quality of RCTs in functional neurosurgery has improved over time but reporting of specific metrics such as power calculations and allocation concealment requires further improvement. Device approval status but not funding source was associated with trial quality.

Long-Term Supratentorial Radiologic Effects of Surgery and Local Radiation in Children with Infratentorial Ependymoma.

BACKGROUND: Current standard of care for children with infratentorial ependymoma includes maximal safe resection and local radiation of 54-59 Gray. High-dose local radiation has been associated with declines in multiple cognitive domains. The anatomic and physiologic correlates of this cognitive decline remain undefined, and there have been no radiographic studies on the long-term effects of this treatment paradigm. METHODS: A comprehensive database of pediatric brain tumor patients treated at Stanford Children's from 2004-2016 was queried. Seven patients with posterior fossa ependymoma who were treated with surgery and local radiation alone, who had no evidence of recurrent disease, and had imaging suitable for analysis were identified. Diffusion-weighted magnetic resonance imaging datasets were used to calculate apparent diffusion coefficient maps for each subject, while arterial spin labeling datasets were used to calculate maps of cerebral blood flow. Diffusion-weighted imaging and arterial spin labeling datasets of 52 age-matched healthy children were analyzed in the same fashion to enable group comparisons. RESULTS: Several statistically significant differences were detected between the 2 groups. Cerebral blood flow was lower in the caudate and pallidum and higher in the nucleus accumbens in the ependymoma cohort compared with controls. Apparent diffusion coefficient was increased in the thalamus and trended toward decreased in the amygdala. CONCLUSIONS: Surgery and local radiation for posterior fossa ependymoma are associated with supratentorial apparent diffusion coefficient and cerebral blood flow alterations, which may represent an anatomic and physiologic correlate to the previously published decline in neurocognitive outcomes in this population.

Contralateral acute vascular occlusion following revascularization surgery for moyamoya disease.

OBJECTIVE: Revascularization surgery is a safe and effective surgical treatment for symptomatic moyamoya disease (MMD) and has been shown to reduce the frequency of future ischemic events and improve quality of life in affected patients. The authors sought to investigate the occurrence of acute perioperative occlusion of the contralateral internal carotid artery (ICA) with contralateral stroke following revascularization surgery, a rare complication that has not been previously reported. METHODS: This study is a retrospective review of a prospective database of a single surgeon's series of revascularization operations in patients with MMD. From 1991 to 2016, 1446 bypasses were performed in 905 patients, 89.6% of which involved direct anastomosis of the superficial temporal artery (STA) to a distal branch of the middle cerebral artery (MCA). Demographic, surgical, and radiographic data were collected prospectively in all treated patients. RESULTS: Symptomatic contralateral hemispheric infarcts occurred during the postoperative period in 34 cases (2.4%). Digital subtraction angiography (DSA) was performed in each of these patients. In 8 cases (0.6%), DSA during the immediate postoperative period revealed associated new occlusion of the contralateral ICA. In each of these cases, revascularization surgery involved direct anastomosis of the STA to an M4 branch of the MCA. Preoperative DSA revealed moderate (n = 1) or severe (n = 3) stenosis or occlusion (n = 4) of the ipsilateral ICA and mild (n = 2), moderate (n = 4), or severe (n = 2) stenosis of the contralateral ICA. The baseline Suzuki stage was 4 (n = 7) or 5 (n = 1). The collateral supply originated exclusively from the intracranial circulation in 4/8 patients (50%), and from both the intracranial and extracranial circulation in the remaining 50% of patients. Seven (88%) of 8 patients improved symptomatically during the acute postoperative period with induced hypertension. The modified Rankin Scale (mRS) score at discharge was worse than baseline in 7/8 patients (88%), whereas 1 patient had only minor deficits that did not affect the mRS score. At the 3-year follow-up, 3/8 patients (38%) were at their baseline mRS score or better, 1 patient had significant disability compared with preoperatively, 2 patients had died, and 1 patient was lost to follow-up. Three-year follow-up is not yet available in 1 patient. CONCLUSIONS: Acute occlusion of the ICA on the contralateral side from an STA-MCA bypass is a rare, but potentially serious, complication of revascularization surgery for MMD. It highlights the importance of the hemodynamic interrelationships that exist between the two hemispheres, a concept that has been previously underappreciated. Induced hypertension during the acute period may provide adequate cerebral blood flow via developing collateral vessels, and good outcomes may be achieved with aggressive supportive management and expedited contralateral revascularization.

Publisher Correction: Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma.

The original version of this Article omitted Suzana A. Kahn, Siddhartha S. Mitra & Samuel H. Cheshier as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article.

Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma.

Medulloblastoma is the most common malignant brain tumor of childhood. Group 3 medulloblastoma, the most aggressive molecular subtype, frequently disseminates through the leptomeningeal cerebral spinal fluid (CSF) spaces in the brain and spinal cord. The mechanism of dissemination through the CSF remains poorly understood, and the molecular pathways involved in medulloblastoma metastasis and self-renewal are largely unknown. Here we show that NOTCH1 signaling pathway regulates both the initiation of metastasis and the self-renewal of medulloblastoma. We identify a mechanism in which NOTCH1 activates BMI1 through the activation of TWIST1. NOTCH1 expression and activity are directly related to medulloblastoma metastasis and decreased survival rate of tumor-bearing mice. Finally, medulloblastoma-bearing mice intrathecally treated with anti-NRR1, a NOTCH1 blocking antibody, present lower frequency of spinal metastasis and higher survival rate. These findings identify NOTCH1 as a pivotal driver of Group 3 medulloblastoma metastasis and self-renewal, supporting the development of therapies targeting this pathway.

Surgical outcomes of pediatric spinal cord astrocytomas: systematic review and meta-analysis.

OBJECTIVE: Pediatric spinal astrocytomas are rare spinal lesions that pose unique management challenges. Therapeutic options include gross-total resection (GTR), subtotal resection (STR), and adjuvant chemotherapy or radiation therapy. With no randomized controlled trials, the optimal management approach for children with spinal astrocytomas remains unclear. The aim of this study was to conduct a systematic review and meta-analysis on pediatric spinal astrocytomas. METHODS: The authors performed a systematic review of the PubMed/MEDLINE electronic database to investigate the impact of histological grade and extent of resection on overall survival among patients with spinal cord astrocytomas. They retained publications in which the majority of reported cases included astrocytoma histology. RESULTS: Twenty-nine previously published studies met the eligibility criteria, totaling 578 patients with spinal cord astrocytomas. The spinal level of intramedullary spinal cord tumors was predominantly cervical (53.8%), followed by thoracic (40.8%). Overall, resection was more common than biopsy, and GTR was slightly more commonly achieved than STR (39.7% vs 37.0%). The reported rates of GTR and STR rose markedly from 1984 to 2015. Patients with high-grade astrocytomas had markedly worse 5-year overall survival than patients with low-grade tumors. Patients receiving GTR may have better 5-year overall survival than those receiving STR. CONCLUSIONS: The authors describe trends in the management of pediatric spinal cord astrocytomas and suggest a benefit of GTR over STR for 5-year overall survival.

Neurosurgical Randomized Controlled Trials-Distance Travelled.

BACKGROUND: The evidence base for many neurosurgical procedures has been limited. We performed a comprehensive and systematic analysis of study design, quality of reporting, and trial results of neurosurgical randomized controlled trials (RCTs). OBJECTIVE: To systematically assess the design and quality characteristics of neurosurgical RCTs. METHODS: From January 1961 to June 2016, RCTs with >5 patients assessing any 1 neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. RESULTS: The median sample size in the 401 eligible RCTs was 73 patients with a mean patient age of 49.6. Only 111 trials (27.1%) described allocation concealment, 140 (34.6%) provided power calculations, and 117 (28.9%) were adequately powered. Significant efficacy or trend for efficacy was claimed in 226 reports (56.4%), no difference between the procedures was found in 166 trials (41.4%), and significant harm was reported in 9 trials (2.2%). Trials with a larger sample size were more likely to report randomization mode, specify allocation concealment, and power calculations (all P < .001). Government funding was associated with better specification of power calculations (P = .008) and of allocation concealment (P = .026), while industry funding was associated with reporting significant efficacy (P = .02). Reporting of funding, specification of randomization mode and primary outcomes, and mention of power calculations improved significantly (all, P < .05) over time. CONCLUSION: Several aspects of the design and reporting of RCTs on neurosurgical procedures have improved over time. Better powered and accurately reported trials are needed in neurosurgery to deliver evidence-based care and achieve optimal outcomes.

Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors.

Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic agent for managing multiple pediatric central nervous system malignancies.

Stereotactic radiosurgery for metastasis to the craniovertebral junction preserves spine stability and offers symptomatic relief.

OBJECT Metastatic disease to the craniovertebral junction (CVJ) is rare but presents unique management challenges. To date, studies on using stereotactic radiosurgery (SRS) for CVJ metastases have been limited to case reports and small case series. The aim of this analysis was to evaluate the utility of SRS in the management of these secondary lesions. METHODS Clinical and radiological information from the charts of 25 patients with metastatic disease of the CVJ who were treated with SRS between 2005 and 2013 at the Stanford CyberKnife Center were retrospectively reviewed. RESULTS Seven male and 18 female patients with a median age of 58 years (range 34-94 years) were identified. The most common primary tumors were breast cancer (n = 5) and non-small cell lung cancer (n = 5), and the most frequent symptom was neck pain (n = 17). The average tumor volume treated was 15.9 cm3 (range 0.16-54.1 cm3), with a mean marginal radiation dose of 20.3 Gy (range 15-25.5 Gy). The median follow-up was 18 months (range 1-81 months), though 1 patient was lost to follow-up. SRS provided radiographic tumor stability in over 80% of patients, offered pain alleviation in nearly two-thirds of patients, and produced no serious complications. Moreover, SRS preserved spinal stability in all but 1 patient, in whom pre-SRS stability was established. There was no evidence of radiation toxicity in the patient population. Median survival was 28 months (range 2-81 months), with survival of 13.3% at 5 years. CONCLUSIONS In the absence of unstable pathological fracture and spinal cord compression, metastatic tumors of the CVJ can be safely and effectively treated with SRS. This treatment option offers palliative pain relief and can halt tumor progression with only a low risk of complications or spinal instability.

Neural Placode Tissue Derived From Myelomeningocele Repair Serves as a Viable Source of Oligodendrocyte Progenitor Cells.

BACKGROUND: The presence, characteristics, and potential clinical relevance of neural progenitor populations within the neural placodes of myelomeningocele patients remain to be studied. Neural stem cells are known to reside adjacent to ependyma-lined surfaces along the central nervous system axis. OBJECTIVE: Given such neuroanatomic correlation and regenerative capacity in fetal development, we assessed myelomeningocele-derived neural placode tissue as a potentially novel source of neural stem and progenitor cells. METHODS: Nonfunctional neural placode tissue was harvested from infants during the surgical repair of myelomeningocele and subsequently further analyzed by in vitro studies, flow cytometry, and immunofluorescence. To assess lineage potential, neural placode-derived neurospheres were subjected to differential media conditions. Through assessment of platelet-derived growth factor receptor α (PDGFRα) and CD15 cell marker expression, Sox2+Olig2+ putative oligodendrocyte progenitor cells were successfully isolated. RESULTS: PDGFRαCD15 cell populations demonstrated the highest rate of self-renewal capacity and multipotency of cell progeny. Immunofluorescence of neural placode-derived neurospheres demonstrated preferential expression of the oligodendrocyte progenitor marker, CNPase, whereas differentiation to neurons and astrocytes was also noted, albeit to a limited degree. CONCLUSION: Neural placode tissue contains multipotent progenitors that are preferentially biased toward oligodendrocyte progenitor cell differentiation and presents a novel source of such cells for use in the treatment of a variety of pediatric and adult neurological disease, including spinal cord injury, multiple sclerosis, and metabolic leukoencephalopathies.

Glioblastoma stem cells and stem cell-targeting immunotherapies.

Advancements in immunotherapeutics promise new possibilities for the creation of glioblastoma (GBM) treatment options. Ongoing work in cancer stem cell biology has progressively elucidated the role of this tumor sub-population in oncogenesis and has distinguished them as prime therapeutic targets. Current clinical trials take a multifaceted approach with the intention of harnessing the intrinsic cytotoxic capabilities of the immune system to directly target glioblastoma cancer stem cells (gCSC) or indirectly disrupt their stromal microenvironment. Monoclonal antibodies (mAbs), dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) T cell therapies have emerged as the most common approaches, with particular iterations incorporating cancer stem cell antigenic markers in their treatment designs. Ongoing work to determine the comprehensive antigenic profile of the gCSC in conjunction with efforts to counter the immunosuppressive tumor microenvironment holds much promise in future immunotherapeutic strategies against GBM. Given recent advancements in these fields, we believe there is tremendous potential to improve outcomes of GBM patients in the continuing evolution of immunotherapies targeted to cancer stem cell populations in GBM.