Current and future directions in interventional neuro-oncology-are we there yet?

Advancements in technology and technical expertise increasingly enable neurointerventionalists to deliver safer and more effective endovascular treatments to cancers of the brain, spine, head, and neck. In addition to established neuro-oncological interventions such as pre-surgical tumor embolization and percutaneous ablation, newer modalities focused on direct arterial infusion of chemotherapy, radioisotopes, and radiosensitizers continue to gain traction as complementary treatment options, while stem cell-mediated delivery of theranostic nanoparticles and oncolytic virus are being explored for even greater specificity in targeting cancers across the blood-brain barrier. This article aims to provide an overview of the current state of the art and future directions for the field of interventional neuro-oncology, as well as opportunities and challenges presented by this emerging treatment modality.

Direct superficial temporal artery access for middle meningeal artery embolization.

Middle meningeal artery embolization has become an important option in the management of subdural hemorrhages with multiple prospective studies demonstrating efficacy and randomized controlled trial data on the way. Access to the middle meningeal artery is usually achieved via the external carotid artery to the internal maxillary artery, then the middle meningeal artery. We report a case where a patient with symptomatic left-sided chronic subdural hemorrhage also had an external carotid artery occlusion. Direct puncture of the superficial temporal artery allowed retrograde access to the internal maxillary artery and thus the middle meningeal artery. Successful embolization of the vessel with 1:9 nBCA was performed with near total resorption of the subdural collection by 1 month postprocedure.

Automated catheter segmentation and tip detection in cerebral angiography with topology-aware geometric deep learning.

BACKGROUND: Visual perception of catheters and guidewires on x-ray fluoroscopy is essential for neurointervention. Endovascular robots with teleoperation capabilities are being developed, but they cannot 'see' intravascular devices, which precludes artificial intelligence (AI) augmentation that could improve precision and autonomy. Deep learning has not been explored for neurointervention and prior works in cardiovascular scenarios are inadequate as they only segment device tips, while neurointervention requires segmentation of the entire structure due to coaxial devices. Therefore, this study develops an automatic and accurate image-based catheter segmentation method in cerebral angiography using deep learning. METHODS: Catheters and guidewires were manually annotated on 3831 fluoroscopy frames collected prospectively from 40 patients undergoing cerebral angiography. We proposed a topology-aware geometric deep learning method (TAG-DL) and compared it with the state-of-the-art deep learning segmentation models, UNet, nnUNet and TransUNet. All models were trained on frontal view sequences and tested on both frontal and lateral view sequences from unseen patients. Results were assessed with centerline Dice score and tip-distance error. RESULTS: The TAG-DL and nnUNet models outperformed TransUNet and UNet. The best performing model was nnUNet, achieving a mean centerline-Dice score of 0.98 ±0.01 and a median tip-distance error of 0.43 (IQR 0.88) mm. Incorporating digital subtraction masks, with or without contrast, significantly improved performance on unseen patients, further enabling exceptional performance on lateral view fluoroscopy despite not being trained on this view. CONCLUSIONS: These results are the first step towards AI augmentation for robotic neurointervention that could amplify the reach, productivity, and safety of a limited neurointerventional workforce.

A rare case of solitary, isolated dural metastasis from hepatocellular carcinoma mimicking a meningioma.

Background: Distinguishing an isolated metastatic dural tumor from a meningioma on imaging is challenging and may lead to a delay in treatment. Here, we present the first known case of isolated, solitary dural metastasis from hepatocellular carcinoma (HCC) mimicking a meningioma. Case Description: A 64-year-old male with a history of liver cirrhosis presented with a 5.8 cm enhancing left parafalcine hemorrhagic dural-based mass extending across the midline. Cerebral angiography revealed a distal left anterior pseudoaneurysm, and tumor contrast blush with feeders from the left ophthalmic and right middle meningeal artery. The pseudoaneurysm was successfully embolized to stop the bleeding, followed by an uneventful bi-coronal frontal craniotomy for falcine tumor resection to relieve brain compression. Histopathological analysis of the dural-based tumor showed poorly differentiated carcinoma with positive albumin in situ hybridization and cytokeratin tumor markers, consistent with dural metastases from HCC. Conclusion: When encountering a solitary, highly vascular mass bearing resemblance to a meningioma, it may be prudent to consider the possibility of a dural-based metastatic carcinoma.

Pleural effusion and respiratory compromise from spontaneous migration of a ventriculoperitoneal shunt catheter in a patient with normal-pressure hydrocephalus.

Background: Ventriculoperitoneal shunt (VPS) insertion is one of the most common neurosurgical procedures done around the world to treat hydrocephalus. The occurrence of spontaneous migration of the peritoneal shunt catheter into the thoracic cavity is a very rare complication; we report here case number 27 of respiratory complications of a VPS in a patient with normal-pressure hydrocephalus (NPH). Case Description: A 76-year-old woman with Alzheimer's disease and anosognosia was diagnosed idiopathic NPH treated surgically with a VPS. Pleural effusion and pulmonary complications occurred 4 weeks after the insertion of the shunt due to the spontaneous migration of the peritoneal catheter of the VPS into the thoracic cavity. The hydrothorax of cerebrospinal fluid was drained and the distal catheter was removed and replaced. The patient made an uneventful recovery. Conclusion: Due to the rarity of this complication, there are no standard corrective procedures. Some of the methods used to diagnose and successfully treat this rare complication of the VPS are presented.

Feasibility and Efficacy of Low-profile Visual Intraluminal Support Device: A Single Center Five-year Experience.

INTRODUCTION: The Low-Profile Visualized Intraluminal Support (LVIS) devices are a new generation of self-expandable, high-porosity stents approved for the treatment of large to giant wide-necked intracranial aneurysms via stent-assisted coiling. Here we report the radiographic and clinical outcomes seen with LVIS, LVIS Jr. and LVIS Blue from a single institution over a fiveyear period. METHODS: Patients with intracranial aneurysms treated by LVIS, LVIS Jr. and LVIS Blue technology over a five-year period (2012 - 2017) at our institution were retrospectively reviewed. RESULTS: Seventy-four patients (55 females and 19 males; average age = 59.2) with 74 aneurysms underwent embolization of intracranial aneurysms using LVIS (N = 10), LVIS Jr. (N = 47) or LVIS Blue (N = 12) devices at our institution over the study period. The most common location of treated aneurysms was the anterior communicating artery (31%), followed by the basilar artery (19%), and the middle cerebral artery (13%). The mean neck and dome sizes were 3.9±1.5mm and 6.6±3.2mm, respectively. The median follow-up time was 6 months. At the last radiographic follow- up, 93.1% of patients had complete occlusion (RR-I or OKM-D). In 5 cases (7%), the LVIS stent failed to open, requiring balloon angioplasty (N = 3) or stent recapture and use of a non-LVIS branded device (N = 2). Five patients had post-embolization infarcts, and 1 patient had an intra-operative dome rupture. CONCLUSION: LVIS brand of stents is a safe, effective, and technically feasible treatment strategy for wide-neck intracranial aneurysms, with high deployment success and aneurysm obliteration rates.

Posteroinferior Cerebellar Artery Aneurysms: Influence of Angioanatomy on the Safety of Flow Diversion Treatment.

Several anatomical variables critically influence therapeutic strategies for posteroinferior cerebellar artery (PICA) aneurysms and, specifically, the safety of flow diversion for these lesions. We review the microsurgical anatomy of the PICA, discussing and detailing these considerations in the treatment of aneurysms of this vessel from a theoretical perspective and in light of our previously published clinical results.

GBM skin metastasis: a case report and review of the literature.

Glioblastoma (GBM) is the most common type of malignant tumor found in the brain, and acts very aggressively by quickly and diffusely infiltrating the surrounding brain parenchyma. Despite its aggressive nature, GBM is rarely found to spread extracranially and develop distant metastases. The most common sites of these rare metastases are the lungs, pleura and cervical lymph nodes. There are also a few case reports of skin metastasis. We present the clinical, imaging and pathologic features of a case of a GBM with metastasis to the soft tissue scar and skin near the original craniotomy site. In addition, we discuss the details of this case in the context of the previously reported literature.

Four-Dimensional Phase Contrast Magnetic Resonance Imaging Protocol Optimization Using Patient-Specific 3-Dimensional Printed Replicas for In Vivo Imaging Before and After Flow Diverter Placement.

OBJECTIVE: Hemodynamics in cerebral aneurysms are currently investigated toward clinical efficacy using nonstandardized computational simulation techniques. At the same time, flow patterns and velocities are accessible by 4-dimensional phase contrast magnetic resonance imaging (4D pcMRI). Complexity of protocol design and imaging duration has limited the use of this technique in clinical imaging. A new approach is presented to overcome these limitations. METHODS: Three-dimensional (3D) replicas of 2 cerebral aneurysms were fabricated by fused deposition prototyping (3D printing) and imaged using 4D pcMRI while connected to a magnetic resonance imaging-compatible continuous flow loop. Acquisition parameters were optimized with imaging times not to exceed 10 minutes. Six patients harboring cerebral aneurysms with sizes ranging from 4.7 to 13.8 mm were imaged with the optimized 4D pcMRI protocol. After treatment with the pipeline embolization device (PED), 4D pcMRI examinations were repeated in 3 patients. RESULTS: In all cases, major flow patterns were visualized well; smaller aneurysms posed a challenge because of limited spatial resolution, whereas larger aneurysms contained regions of low velocity resulting in limited contrast in the flow-sensitive images. After PED placement, ordered aneurysmal flow was disrupted and intra-aneurysmal velocity was reduced on average by 24.5% (range, 12.9-31.5%). Exploratory statistical analysis yielded a positive significant correlation (P < 0.01) between changes in inflow velocity and posttreatment intra-aneurysmal flow velocity. CONCLUSIONS: 4D pcMRI flow imaging in cerebral aneurysms within a time frame suitable for clinical imaging applications is feasible with optimized acquisition parameters, thereby enabling quantification of intra-aneurysmal flow changes after flow diverter device treatment.

HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial.

IMPORTANCE: Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. OBJECTIVE: To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. DESIGN, SETTING, AND PARTICIPANTS: In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was 10 weeks to 29 months (median, 8 months). INTERVENTIONS: Monotherapy with autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs with a CD28.ζ-signaling endodomain (HER2-CAR VSTs). MAIN OUTCOMES AND MEASURES: Primary end points were feasibility and safety. The key secondary end points were T-cell persistence and their antiglioblastoma activity. RESULTS: A total of 17 patients (8 females and 9 males; 10 patients ≥18 years [median age, 60 years; range, 30-69 years] and 7 patients <18 years [median age, 14 years; range, 10-17 years]) with progressive HER2-positive glioblastoma received 1 or more infusions of autologous HER2-CAR VSTs (1 × 106/m2 to 1 × 108/m2) without prior lymphodepletion. Infusions were well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected in the peripheral blood for up to 12 months after the infusion by quantitative real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7 children), 1 had a partial response for more than 9 months, 7 had stable disease for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients with stable disease are alive without any evidence of progression during 24 to 29 months of follow-up. For the entire study cohort, median overall survival was 11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5 months (95% CI, 17.2-34.6 months) from diagnosis. CONCLUSIONS AND RELEVANCE: Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical benefit for patients with progressive glioblastoma. Further evaluation of HER2-CAR VSTs in a phase 2b study is warranted as a single agent or in combination with other immunomodulatory approaches for glioblastoma.

Middle cerebral artery aneurysms: a single-center series comparing endovascular and surgical treatment.

OBJECTIVE: The optimal treatment for middle cerebral artery (MCA) aneurysms is controversial. MCA aneurysms have been considered more conducive to surgical treatment. Recent technology has led to successful endovascular treatment of MCA aneurysms. The objective of this study was to analyze the outcomes of endovascular and surgical treatment of MCA aneurysms as experienced by a single tertiary center. METHODS: We retrospectively reviewed 90 MCA aneurysms in 84 patients treated from 2005 to 2010. They were separated into 2 groups: endovascular coiling, with 50 (59.5%) patients, and surgical clipping, with 34 (40.5%) patients. Outcome was based on complications, procedural morbidity and mortality, clinical and angiographic outcomes, and retreatment rates. Patients were further separated into ruptured and unruptured aneurysm groups. RESULTS: Ruptured aneurysms were 10 of 50 (20%) and 9 of 34 (26.5%) patients in the endovascular and surgical groups, respectively. Procedure-related complications were 16% and 0% for the endovascular and surgical groups (P = .01), respectively. Overall rate of complete or near-complete occlusion at angiographic follow-up was 86% and 95% for the endovascular and surgical groups (P = .16), respectively. Proportion of patients with modified Rankin scale of 3 to 6 at 6 months follow-up was 10% and 5.9% for the endovascular and surgical groups (P = .5), respectively. The mean angiographic follow-up was 9.02 months (range 0 to 5.2 years). Retreatment rates were 14% and 0% for the endovascular and surgical groups, respectively (P = .01). CONCLUSIONS: In this nonrandomized sample of 90 MCA aneurysms treated with endovascular coiling or neurosurgical clipping, we observed a similar clinical outcome based on the modified Rankin scale and angiographic occlusion. Complication and retreatment rates were higher but not significant for the endovascular group. Both treatment modalities are good alternatives and should be individualized based on aneurysm angioarchitecture and the patient's general conditions.

Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma.

Preclinical and early clinical studies have demonstrated that chimeric antigen receptor (CAR)-redirected T cells are highly promising in cancer therapy. We observed that targeting HER2 in a glioblastoma (GBM) cell line results in the emergence of HER2-null tumor cells that maintain the expression of nontargeted tumor-associated antigens. Combinational targeting of these tumor-associated antigens could therefore offset this escape mechanism. We studied the single-cell coexpression patterns of HER2, IL-13Rα2, and EphA2 in primary GBM samples using multicolor flow cytometry and immunofluorescence, and applied a binomial routine to the permutations of antigen expression and the related odds of complete tumor elimination. This mathematical model demonstrated that cotargeting HER2 and IL-13Rα2 could maximally expand the therapeutic reach of the T cell product in all primary tumors studied. Targeting a third antigen did not predict an added advantage in the tumor cohort studied. We therefore generated bispecific T cell products from healthy donors and from GBM patients by pooling T cells individually expressing HER2 and IL-13Rα2-specific CARs and by making individual T cells to coexpress both molecules. Both HER2/IL-13Rα2-bispecific T cell products offset antigen escape, producing enhanced effector activity in vitro immunoassays (against autologous glioma cells in the case of GBM patient products) and in an orthotopic xenogeneic murine model. Further, T cells coexpressing HER2 and IL-13Rα2-CARs exhibited accentuated yet antigen-dependent downstream signaling and a particularly enhanced antitumor activity.

The role of endoscopic third ventriculostomy in the treatment of communicating hydrocephalus.

OBJECTIVE: To elucidate the role of endoscopic third ventriculostomy (ETV) in patients with secondary and idiopathic communicating hydrocephalus (HCP). METHODS: A series of 36 patients with communicating HCP (21 men and 15 women) were treated by ETV between November 2007 and February 2010. The patients age ranged from 19 to 81 years old (mean 52 years), and had a follow-up of 6 to 36 months (mean 9.2 months). The patients were divided into a group of 29 patients with secondary communicating HCP and a group of 7 patients with normal pressure HCP. Sixteen (44.4%) of the patients had a previous ventriculoperitoneal shunt placement that presented with shunt malfunction. RESULTS: The etiology of secondary HCP was subarachnoid hemorrhage, meningitis, trauma, neoplasm, and others. Etiology was not possible to determine in some patients. The outcome of ETV was considered successful in 27/36 patients (75%). A Kaplan-Meier analysis revealed that the successful proportion of ETVs in secondary communicating HCP at 0.5, 1, and 3 months of follow-up was 0.83, 0.8, and 0.77, respectively; in the idiopathic normal pressure HCP group it was 0.83 initially and became stable at 0.66 after the first month. Overall, the successful proportion of ETV in communicating HCP was at 0, 0.5, 1, and 3 months of follow-up was 0.97, 0.83, 0.78, and 0.75. CONCLUSIONS: ETV is a good option in the management of secondary communicating HCP, normal pressure HCP, and replacing malfunctioning ventriculoperitoneal shunts. The indications of ETV as a first-line treatment in communicating HCP needs further study; however, results are promising.

Neuroendoscopic diagnosis of central nervous system histoplasmosis with basilar arachnoiditis.

OBJECTIVE: Histoplasmosis of the central nervous system (CNS) is seen in 10% to 20% of patients with disseminated histoplasmosis and/or in association with immunocompromised patients. Meningitis, arachnoiditis, and hydrocephalus are the most common clinical manifestations of CNS histoplasmosis. Patients with CNS histoplasmosis present similarly to other infectious etiologies, and confirmatory diagnosis is important in the management of these patients. However, diagnosis of CNS histoplasmosis can be difficult, and sometimes performing a parenchymal biopsy is necessary to confirm the diagnosis. METHODS AND RESULTS: We describe the case of a 41-year-old man with HIV/AIDS who presented with the signs, symptoms, and radiologic evidence of basal meningitis and hydrocephalus. Cerebrospinal fluid (CSF) analysis from multiple lumbar punctures was negative. The patient underwent a neuroendoscopic procedure with diagnostic and therapeutic goals. Internal CSF diversion (endoscopic third ventriculostomy) and biopsy of the floor of the third ventricle and subarachnoid space were performed; surgical biopsies identified noncaseating granulomas, and ventricular CSF was positive for Histoplasmosis antibodies. The patient was treated with liposomal amphotericin B and itraconazole. The patient had resolution of his symptoms immediately after surgery, and 1-month follow-up computed tomography of the head demonstrated resolution of the hydrocephalus. At the last follow-up 12 months postoperatively, the patient has not required insertion of a ventriculoperitoneal shunt. CONCLUSION: Clinicians should maintain a high index of suspicion for fungal basal meningitis in patients with AIDS and hydrocephalus. With nondiagnostic lumbar CSF sampling, neuroendoscopy can be considered as an alternative for diagnosis and treatment of basal meningitis and hydrocephalus.

Desmoplastic non-infantile ganglioglioma in late adulthood.

Desmoplastic infantile ganglioglioma (DIG) is an uncommon supratentorial neuroepithelial brain tumor that typically occurs in infants younger than 24 months. Desmoplastic non-infantile ganglioglioma (DNIG) is a rare variant of this intracranial neoplasm. There are only 16 DNIG cases reported in the literature, with all patients under the age of 25 at the time of presentation. These DIG and DNIG cases were radiologically and histologically similar, with good outcome after treatment. Despite the size and high mitotic index for patients with DNIG, the prognosis is generally favorable and gross total resection is sufficient. We present a case of a 59-year-old woman with a DNIG. To the best of our knowledge, this is the first case reported of DNIG in late adulthood. Clinical presentation, histological and radiological findings are discussed.

Dissemination of prostate adenocarcinoma to the skull base mimicking giant trigeminal schwannoma: anatomic relevance of the extradural neural axis component.

We report an unusual case of a large metastatic lesion from prostate adenocarcinoma with its epicenter located in Meckel's cave. The patient presented with acute neurological deterioration due to pontomesencephalic, cranial nerve, and temporal lobe compression. This lesion radiologically mimicked a giant trigeminal schwannoma. Complete surgical resection was achieved with improvement in the performance status of the patient. The anatomic relevance the extradural neural axis component in the process of dissemination of prostate adenocarcinoma to the skull base is highlighted.