Graft stenosis and occlusion remain formidable complications in cerebral revascularization procedures, which can lead to significant morbidity and mortality. Graft vasospasm can result in early postoperative graft stenosis and occlusion and is believed to be at least partially mediated through adrenergic pathways. Despite various published treatment protocols, there is no single effective spasmolytic agent. Multiple factors, including anatomical and physiological variability in revascularization conduits, patient age, and comorbidities, have been associated with graft vasospasm pathogenesis and response to spasmolytics. The ideal spasmolytic agent thus likely needs to target multiple pathways to exert a generalizable therapeutic effect. Botulinum toxin (BTX)–A is a powerful neurotoxin widely used in clinical practice for the treatment of a variety of spastic conditions. Although its commonly described paradigm of cholinergic neural transmission blockade has been widely accepted, evidence for other mechanisms of action including inhibition of adrenergic transmission have been described in animal studies. Recently, the first pilot study demonstrating clinical use of BTX-A for cerebral revascularization graft spasm prevention has been reported. In this review, the mechanistic basis and potential future clinical role of BTX-A in graft vasospasm prevention is discussed.
Kristine Ravina, Ben A. Strickland, Robert C. Rennert, Joseph N. Carey and Jonathan J. Russin
Robert C. Rennert, Reid R. Hoshide, Jason W. Signorelli, Deirdre Amaro, Jayson A. Sack, Cameron W. Brennan and Clark C. Chen
The authors report an unusual case of a widely metastatic glioblastoma. DNA copy number microarray profile of the resected specimen revealed complex rearrangements found throughout chromosome 6, a phenomenon known as chromothripsis. Such chromothripsis pattern was not observed in 50 nonmetastatic glioblastoma specimens analyzed. Analysis of the 1000+ gliomas profiled by The Cancer Genome Atlas (TCGA) data set revealed one case of chromosome 6 chromothripsis resembling the case described here. This TCGA patient died within 6 months of undergoing tumor resection. Implications of these findings are reviewed in the context of the current literature.
Robert C. Rennert, Kate T. Carroll, Mir Amaan Ali, Thomas Hamelin, Leon Chang, Brian P. Lemkuil and Clark C. Chen
Stereotactic laser ablation (SLA) is typically performed in the setting of intraoperative MRI or in a staged manner in which probe insertion is performed in the operating room and thermal ablation takes place in an MRI suite.
The authors describe their experience, in which SLA for glioblastoma (GBM) treatment was performed entirely within a conventional MRI suite using the SmartFrame stereotactic device.
All 10 patients with GBM (2 with isocitrate dehydrogenase 1 mutation [mIDH1] and 8 with wild-type IDH1 [wtIDH1]) were followed for > 6 months. One of these patients underwent 2 independent SLAs approximately 12 months apart. Biopsies were performed prior to SLA for all patients. There were no perioperative morbidities, wound infections, or unplanned 30-day readmissions. The average time for a 3-trajectory SLA (n = 3) was 436 ± 102 minutes; for a 2-trajectory SLA (n = 4) was 321 ± 85 minutes; and for a single-trajectory SLA (n = 4) was 254 ± 28 minutes. No tumor recurrence occurred within the blue isotherm line ablation zone, although 2 patients experienced recurrence immediately adjacent to the blue isotherm ablation line. Overall survival for the patient cohort averaged 356 days, with the 2 patients who had mIDH1 GBMs exhibiting the longest survival (811 and 654 days).
Multitrajectory SLA for treatment of GBM can be safely performed using the SmartFrame stereotactic device in a conventional MRI suite.
Robert C. Rennert, Danielle M. Levy, Jillian Plonsker, Jeffrey A. Steinberg, Rick A. Friedman, John R. Crawford and Michael L. Levy
Pediatric cerebellopontine angle (CPA) meningiomas are extremely rare and are usually treated with a retrosigmoid surgical approach or radiation. The authors present the use of a middle fossa approach for the treatment of a symptomatic CPA meningioma in a 22-month-old female. The patient initially presented at 17 months with isolated progressive, long-standing right-sided facial weakness. MRI demonstrated a 5.0 × 5.0–mm right CPA lesion just superior to the cisternal segment of cranial nerve (CN) VII, which demonstrated growth on interval imaging. At 22 months of age she underwent a successful middle fossa craniotomy, including wide exposure of the porus acusticus, allowing for a gross-total resection with preservation of CNs VII and VIII. Pathological analysis revealed a WHO grade I meningioma. The patient remained neurologically stable on follow-up. The middle fossa approach can be used to safely access the CPA in properly selected pediatric patients.
Kristine Ravina, Robert C. Rennert, Ben A. Strickland, Mark Chien, Joseph N. Carey and Jonathan J. Russin
Moyamoya disease (MMD) is a progressive, idiopathic cerebrovascular occlusive disease. Various revascularization techniques including direct, indirect, and combined microvascular bypasses have been described. This article presents a modified revascularization technique for MMD utilizing a pedicled temporoparietal fascial flap (TPFF) for combined revascularization. This technique combines a large area of coverage for indirect revascularization with the benefits of a direct bypass. The pedicled TPFF also benefits from intact venous drainage to minimize the risk of flap swelling that could result in complications from mass effect.
Kristine Ravina, Ben A. Strickland, Robert C. Rennert, Vance Fredrickson, Joshua Bakhsheshian, Mark Chien, William Mack, Arun Amar and Jonathan J. Russin
Fusiform aneurysms of the vertebral artery (VA) involving the posterior inferior cerebellar artery (PICA) origin are uncommon and challenging. The anterior spinal artery (ASA) commonly originates from a unilateral ramus just distal to the PICA. Occlusion of an unpaired ASA can result in bilateral medial medullary syndrome. The authors propose a treatment paradigm for ASA preservation based on the artery’s proximity to fusiform VA aneurysms, and they present 3 representative cases. In the first case, they performed a V3-PICA bypass using an interposition graft and then performed endovascular coil embolization of the parent VA. A complete occlusion of the aneurysm and VA was complicated by ASA thrombosis. The subsequent cases were treated with PICA-PICA bypass and subsequent endovascular embolization of the VA. Filling of the sole angiographic ASA remote from the aneurysm was preserved in both cases. The anatomy of the ASA is the most critical determinant of treatment recommendations for fusiform VA aneurysms involving PICA. When the ASA originates from the aneurysm, proximal occlusion with or without a PICA bypass is suggested. In cases in which the ASA is removed from the aneurysm, the authors recommend revascularization followed by endovascular sacrifice. When the aneurysm is immediately adjacent to the ASA, revascularization and open trapping should be considered.
Michael G. Brandel, Robert C. Rennert, Arvin R. Wali, David R. Santiago-Dieppa, Jeffrey A. Steinberg, Christian Lopez Ramos, Peter Abraham, J. Scott Pannell and Alexander A. Khalessi
Preoperative embolization of meningiomas can facilitate their resection when they are difficult to remove. The optimal use and timing of such a procedure remains controversial given the risk of embolization-linked morbidity in select clinical settings. In this work, the authors used a large national database to study the impact of immediate preoperative embolization on the immediate outcomes of meningioma resection.
Meningioma patients who had undergone elective resection were identified in the National (Nationwide) Inpatient Sample (NIS) for the period 2002–2014. Patients who had undergone preoperative embolization were propensity score matched to those who had not, adjusting for patient and hospital characteristics. Associations between preoperative embolization and morbidity, mortality, and nonroutine discharge were investigated.
Overall, 27,008 admissions met the inclusion criteria, and 633 patients (2.34%) had undergone preoperative embolization and 26,375 (97.66%) had not. The embolization group was younger (55.17 vs 57.69 years, p < 0.001) with a lower proportion of females (63.5% vs 69.1%, p = 0.003), higher Charlson Comorbidity Index (p = 0.002), and higher disease severity (p < 0.001). Propensity score matching retained 413 embolization and 413 nonembolization patients. In the matched cohort, preoperative embolization was associated with increased rates of cerebral edema (25.2% vs 17.7%, p = 0.009), posthemorrhagic anemia or transfusion (21.8% vs 13.8%, p = 0.003), and nonroutine discharge (42.8% vs 35.7%, p = 0.039). There was no difference in mortality (≤ 2.4% vs ≤ 2.4%, p = 0.82). Among the embolization patients, the mean interval from embolization to resection was 1.49 days. On multivariate analysis, a longer interval was significantly associated with nonroutine discharge (OR 1.33, p = 0.004) but not with complications or mortality.
Relative to meningioma patients who do not undergo preoperative embolization in the same admission, those who do have higher rates of cerebral edema and nonroutine discharge but not higher rates of stroke or death. Thus, meningiomas requiring preoperative embolization represent a distinct clinical entity that requires prolonged, more complex care. Further, among embolization patients, the timing of resection did not affect the risk of in-hospital complications, suggesting that the timing of surgery can be determined according to surgeon discretion.
Corey T. Walker, Chiazo S. Amene, Jeffrey S. Pannell, David R. Santiago-Dieppa, Robert C. Rennert, Lawrence A. Hansen and Alexander A. Khalessi
The differential diagnosis of spinal tumors is guided by anatomical location and imaging characteristics. Diagnosis of rare tumors is made challenging by abnormal features. The authors present the case of a 47-year-old woman who presented with progressive subacute right lower-extremity weakness and numbness of the right thigh. Physical examination further revealed an extensor response to plantar reflex on the right and hyporeflexia of the right Achilles and patellar reflexes. Magnetic resonance imaging of the lumbar spine demonstrated an 8-mm intramedullary exophytic nodule protruding into a hematoma within the conus medullaris. Spinal angiography was performed to rule out an arteriovenous malformation, and resection with hematoma evacuation was completed. Pathological examination of the resected mass demonstrated a spindle cell neoplasm with dense bundles of collagen. Special immunostaining was performed and a diagnosis of solitary fibrous tumor (SFT) was made. SFTs are mesenchymally derived pleural neoplasms, which rarely present at other locations of the body, but have been increasingly described to occur as primary neoplasms of the spine and CNS. The authors believe that this case is unique in its rare location at the level of the conus, and also that this is the first report of a hemorrhagic SFT in the spine. Therefore, with this report the authors add to the literature the fact that this variant of an increasingly understood but heterogeneous tumor can occur, and therefore should be considered in the differential of clinically similar tumors.
Ben A. Strickland, Robert C. Rennert, Joshua Bakhsheshian, Sebina Bulic, Adrian J. Correa, Arun Amar, Joseph Carey and Jonathan J. Russin
Surgical revascularization continues to play an important role in the management of complex intracranial aneurysms and ischemic cerebrovascular disease. Graft spasm is a common complication of bypass procedures and can result in ischemia or graft thrombosis. The authors here report on the first clinical use of botulinum toxin to prevent graft spasm following extracranial-intracranial (EC-IC) bypass. This technique was used in 3 EC-IC bypass surgeries, 2 for symptomatic carotid artery occlusions and 1 for a ruptured basilar tip aneurysm. In all 3 cases, the harvested graft was treated ex vivo with botulinum toxin before the anastomosis was performed. Post-bypass vascular imaging demonstrated patency and the absence of spasm in all grafts. Histopathological analyses of treated vessels did not show any immediate endothelial or vessel wall damage. Postoperative angiograms were without graft spasm in all cases. Botulinum toxin may be a reasonable option for preventing graft spasm and maintaining patency in cerebral revascularization procedures.
Peter Abraham, J. Scott Pannell, David R. Santiago-Dieppa, Vincent Cheung, Jeffrey Steinberg, Arvin Wali, Mihir Gupta, Robert C. Rennert, Roland R. Lee and Alexander A. Khalessi
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.
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.
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.
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.