Vincent Cheung

IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection

BACKGROUND IDH1 gene mutations identify gliomas with a distinct molecular evolutionary origin. We sought to determine the impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas-World Health Organization grade III anaplastic astrocytomas and grade IV glioblastoma. METHODS Clinical parameters including volumetric assessment of preoperative and postoperative MRI were recorded prospectively on 335 malignant astrocytoma patients: n = 128 anaplastic astrocytomas and n = 207 glioblastoma. IDH1 status was assessed by sequencing and immunohistochemistry. RESULTS IDH1 mutation was independently associated with complete resection of enhancing disease (93% complete resections among mutants vs 67% among wild-type, P < .001), indicating IDH1 mutant gliomas were more amenable to resection. The impact of residual tumor on survival differed between IDH1 wild-type and mutant tumors. Complete resection of enhancing disease among IDH1 wild-type tumors was associated with a median survival of 19.6 months versus 10.7 months for incomplete resection; however, no survival benefit was observed in association with further resection of nonenhancing disease (minimization of total tumor volume). In contrast, IDH1 mutants displayed an additional survival benefit associated with maximal resection of total tumor volume (median survival 9.75 y for >5 cc residual vs not reached for <5 cc, P = .025). CONCLUSIONS The survival benefit associated with surgical resection differs based on IDH1 genotype in malignant astrocytic gliomas. Therapeutic benefit from maximal surgical resection, including both enhancing and nonenhancing tumor, may contribute to the better prognosis observed in the IDH1 mutant subgroup. Thus, individualized surgical strategies for malignant astrocytoma may be considered based on IDH1 status.

Epidemiology of Metastatic Brain Tumors

Metastatic tumors are the most common brain tumors in adults, and their incidence is increasing. An accurate understanding of the epidemiology of metastatic brain tumors is useful for health care professionals to allocate appropriate clinical, diagnostic, therapeutic, and research resources. Reported incidences in the literature are derived from epidemiologic population-based studies; clinical studies from surgical, radiological, and autopsy series; and reviews of hospital and clinical medical records. Despite these various sources of information, an accurate incidence of metastatic brain tumors is difficult, and current figures are estimates at best. Here, we review the available data regarding the epidemiology of metastatic brain tumors.

Extracellular vesicles as a platform for ‘liquid biopsy’ in glioblastoma patients

Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30–2000 nm in size. These vesicles are secreted by both normal and neoplastic cells. Physiologically, EVs serve multiple critical biologic functions, including cellular remodeling, intracellular communication, modulation of the tumor microenvironment and regulation of immune function. Because EVs contain genetic and proteomic contents that reflect the cell of origin, it is possible to detect tumor-specific material in EVs secreted by cancer cells. Importantly, EVs secreted by cancer cells transgress anatomic compartments and can be detected in the blood, cerebrospinal fluid, and other biofluids of cancer patients. In this context, there is a growing interest in analyzing EVs from the biofluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. In this article, we review the development of EVs as a diagnostic platform for the most common form of brain cancer, glioblastoma, discuss potential clinical translational opportunities and identify the central challenges associated with future clinical applications.

The Cancer Genome Atlas expression profiles of low-grade gliomas

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.

Vessel wall signal enhancement on 3-T MRI in acute stroke patients after stent retriever thrombectomy.

OBJECTIVE In vivo and in vitro studies have demonstrated histological evidence of iatrogenic endothelial injury after stent retriever thrombectomy. However, noncontrast vessel wall (VW)-MRI is insufficient to demonstrate vessel injury. Authors of this study prospectively evaluated iatrogenic endothelial damage after stent retriever thrombectomy in humans by utilizing high-resolution contrast-enhanced VW-MRI. Characterization of VW-MRI changes in vessels subject to mechanical injury from thrombectomy may allow better understanding of the biological effects of this intervention. METHODS The authors prospectively recruited 11 patients for this study. The treatment group included 6 postthrombectomy patients and the control group included 5 subjects undergoing MRI for nonvascular indications. All subjects were evaluated on a Signa HD× 3.0-T MRI scanner with an 8-channel head coil. Both pre- and postcontrast T1-weighted Cube VW images as well as MR angiograms were acquired. Sequences obtained for evaluation of the brain parenchyma included diffusion-weighted, gradient echo, and T2-FLAIR imaging. Two independent neuroradiologists, who were blinded to the treatment status of each patient, determined the presence of VW enhancement. Patient age, National Institutes of Health Stroke Scale score on presentation, location of occlusion, stroke etiology, type of device used, number of device deployments, Thrombolysis in Cerebral Infarction (TICI) reperfusion score, stroke volume, and 90-day modified Rankin Scale score were also noted. RESULTS Postcontrast T1-weighted VW enhancement was detected in the M2 segment in 100% of the thrombectomy patients, in the M1 segment in 83%, and in the internal carotid artery in 50%. One patient also demonstrated A1 segment enhancement, which was attributable to thrombectomy treatment of that vessel segment during the same procedure. None of the control patients demonstrated VW enhancement of their intracranial vasculature on T1-weighted images. CONCLUSIONS The study findings suggest that VW injury incurred during stent retriever thrombectomy can be reliably detected utilizing contrast-enhanced 3-T VW-MRI. The results further demonstrate that endothelial injury is associated with oversizing of stent retrievers relative to the treated vessel. Further studies are needed to evaluate the clinical significance of endothelial injury and to characterize the differential effects of various devices.

302 Vessel Wall Enhancement on Magnetic Resonance Imaging After Stent-Retriever Thrombectomy.

INTRODUCTION Animal and in vitro studies have demonstrated histologic iatrogenic endothelial injury after stent-retriever thrombectomy. However, noncontrast vessel wall magnetic resonance imaging (MRI) studies have failed to demonstrate vessel injury. Our prospective study examines iatrogenic endothelial damage after stent-retriever thrombectomy in vivo utilizing high-resolution contrast-enhanced vessel wall MRI (VW-MRI). METHODS We evaluated 11 patients, including postthrombectomy and control subjects, on a Signa HDx 3.0-T MRI scanner with an 8-channel head coil. Pre- and postcontrast T1-weighted CUBE vessel wall images and MR angiograms were acquired with attention to the Circle of Willis. Parenchymal imaging included diffusion, susceptibility, and T2 fluid attenuated inversion recovery (FLAIR)-weighted images. The primary end point was vessel wall enhancement, as determined by 2 independent, blinded board-certified neuroradiologists before examination of parenchymal imaging. Additional covariates were age, National Institutes of Health Stroke Scale, level of occlusion, stroke etiology, devices utilized, number of passes required for thrombectomy, TICI reperfusion score, stroke volume, and 90-day modified Rankin Scale (mRS). RESULTS Post-contrast T1-weighted vessel wall enhancement was detected in the middle cerebral artery (MCA) M2 segment in 100%, the M1 segment in 83%, and the internal carotid artery in 50% of thrombectomy patients. One patient demonstrated A1 segment anterior cerebral artery (ACA) enhancement, and was prospectively identified by both radiologists as having undergone ACA thrombectomy due to embolism during MCA thrombectomy. Postcontrast T1-weighted vessel wall enhancement was detected in 0% of control patients. CONCLUSION Our findings suggest that vessel wall injuries incurred during stent-retriever thrombectomy can be detected utilizing contrast-enhanced 3 T VW-MRI. Our results further demonstrate greater endothelial injury when the thrombectomy device is oversized relative to the target vessel. Further studies are needed to evaluate the clinical significance of endothelial injury and differential effects of the device employed.

Methylprednisolone in the management of spinal cord injuries: Lessons from randomized, controlled trials.

The efficacy of glucocorticoid for treatment of acute spinal cord injuries remains a controversial topic. Differing medical societies have issued conflicting recommendations in this regard. Here we review the available randomized, controlled trial (RCT) data on this subject and offer a synthesis of these data sets.

Simulator-Based Angiography and Endovascular Neurosurgery Curriculum: A Longitudinal Evaluation of Performance Following Simulator-Based Angiography Training

This study establishes performance metrics for angiography and neuroendovascular surgery procedures based on longitudinal improvement in individual trainees with differing levels of training and experience. Over the course of 30 days, five trainees performed 10 diagnostic angiograms, coiled 10 carotid terminus aneurysms in the setting of subarachnoid hemorrhage, and performed 10 left middle cerebral artery embolectomies on a Simbionix Angio Mentor™ simulator. All procedures were nonconsecutive. Total procedure time, fluoroscopy time, contrast dose, heart rate, blood pressures, medications administered, packing densities, the number of coils used, and the number of stent-retriever passes were recorded. Image quality was rated, and the absolute value of technically unsafe events was recorded. The trainees’ device selection, macrovascular access, microvascular access, clinical management, and the overall performance of the trainee was rated during each procedure based on a traditional Likert scale score of 1=fail, 2=poor, 3=satisfactory, 4=good, and 5=excellent. These ordinal values correspond with published assessment scales on surgical technique. After performing five diagnostic angiograms and five embolectomies, all participants demonstrated marked decreases in procedure time, fluoroscopy doses, contrast doses, and adverse technical events; marked improvements in image quality, device selection, access scores, and overall technical performance were additionally observed (p < 0.05). Similarly, trainees demonstrated marked improvement in technical performance and clinical management after five coiling procedures (p < 0.05). However, trainees with less prior experience deploying coils continued to experience intra-procedural ruptures up to the eighth embolization procedure; this observation likely corresponded with less tactile procedural experience to an exertion of greater force than appropriate for coil placement. Trainees across all levels of training and prior experience demonstrated a significant performance improvement after completion of our simulator curriculum consisting of five diagnostic angiograms, five embolectomy cases, and 10 aneurysm coil embolizations.

Low-profile Visualized Intraluminal Support Junior Device for the Treatment of Intracranial Aneurysms.

Objective: Early case series suggest that the recently introduced Low-profile Visualized Intraluminal Support Junior (LVIS Jr.) device (MicroVention-Terumo, Inc., Tustin, CA) may be used to treat wide-necked aneurysms that would otherwise require treatment with intrasaccular devices or open surgery. We report our single-center experience utilizing LVIS Jr. to treat intracranial aneurysms involving 1.8-2.5 mm parent arteries. Methods: We retrospectively reviewed records of patients treated with the LVIS Jr. device for intracranial aneurysms at a single center. A total of 21 aneurysms were treated in 18 patients. Aneurysms were 2-25 mm in diameter; one was ruptured, while three had recurred after previous rupture and treatment. Lesions were distributed across the anterior (n=12) and posterior (n=9) circulations. Three were fusiform morphology. Results: Stent deployment was successful in 100% of cases with no immediate complications. Seventeen aneurysms were treated with stent-assisted coil embolization resulting in immediate complete occlusion in 94% of cases. Two fusiform aneurysms arising from the posterior circulation were further treated with elective clip ligation after delayed expansion and recurrence; no lesions required further endovascular treatment. Four aneurysms were treated by flow diversion with stand-alone LVIS Jr. stent, and complete occlusion was achieved in three cases. Small foci of delayed ischemic injury were noted in two patients in the setting of antiplatelet medication noncompliance. No in-stent stenosis, migration, hemorrhage, or permanent deficits were observed. Good functional outcome based on the modified Rankin Scale score (mRS ≤ 2) was achieved in 100% of cases. Conclusion: Our midterm results suggest that the LVIS Jr. stent may be used for a variety of intracranial aneurysms involving small parent arteries (1.8-2.5 mm) with complete angiographic occlusion, parent vessel preservation, and functional clinical outcomes. This off-label expansion would increase the number of aneurysms amenable to endovascular treatment. Future studies may build upon our experiences with flow diversion and treatment of complex or multiple lesions.

Do corticosteroids play a role in the management of traumatic brain injury

Neuroprotective strategies for the medical management of traumatic brain injury (TBI) have been elusive. While laboratory studies provide a conceptual framework for the potential efficacy of corticosteroids in this context, clinical trials testing this hypothesis have yielded no convincing evidence of clinical benefit. Here, we review the five key randomized control trials (RCTs) that have examined this issue. Based on the proposed primary endpoints of these RCTs, the five RCTs consistently showed that corticosteroids do not confer significant benefit in the TBI population.