Prospective trial of gross-total resection with Gliadel wafers followed by early postoperative Gamma Knife radiosurgery and conformal fractionated radiotherapy as the initial treatment for patients with radiographically suspected, newly diagnosed glioblastoma multiforme
L. Fernando Gonzalez and Kris A. Smith
Case report and review of the literature
L. Fernando Gonzalez, Ruth E. Bristol, Randall W. Porter and Robert F. Spetzler
✓ The authors report the case of a patient with a de novo arteriovenous malformation (AVM), indicating that the origin of these lesions may not always be congenital.
A 3-year-old girl who was struck by a car suffered a mild head injury and experienced posttraumatic epilepsy. The initial magnetic resonance (MR) image obtained in this child revealed only a small contusion in the left frontal lobe. Intractable epilepsy subsequently developed. A second MR image obtained almost 4 years after the injury demonstrated an AVM in the right posterior temporal lobe that was verified using angiography. The lesion was classified as a Spetzler—Martin Grade III AVM. The patient underwent embolization of the feeding vessels followed by gamma knife surgery. Fourteen months after treatment she was asymptomatic. Follow-up MR images demonstrate no evidence of an AVM and no changes in the white matter.
This case presents a de novo AVM that developed within approximately 4 years. The findings indicate that AVMs may not always be congenital and reinforce the concept that the natural history of AVMs is dynamic. Lesions may appear de novo, grow, and thrombose spontaneously.
L. Fernando Gonzalez, Louis Kim, Harold L. Rekate, Cameron G. Mcdougall and Felipe C. Albuquerque
✓Atrial shunt revision surgeries are sometimes difficult due to venous occlusion and neck scarring. A direct approach guided by venography facilitates exposure and guarantees accurate placement of the distal catheter. Five patients with complicated histories of shunt malfunction were treated using an endoscope-assisted technique. The distal end of an atrial catheter was advanced into the atrium after having been connected to a venous catheter of a slightly smaller diameter than the one previously advanced from the femoral vein through the atrium. Once the position of the atrial catheter was confirmed fluoroscopically, the venous catheter was detached and removed. No complications developed in any patient.
This endoscope-assisted technique offers three advantages: it demonstrates the patency of the jugular vein through venography, facilitates identification of the internal jugular vein in the neck, and provides a quick way to confirm that the distal end of the atrial catheter has been placed correctly. This technique should be considered for use in patients with a history of failed atrial shunts.
Jeffrey S. Henn, G. Michael Lemole Jr., Mauro A. T. Ferreira, L. Fernando Gonzalez, Mark Schornak, Mark C. Preul and Robert F. Spetzler
✓ The goal of this study was to develop a new method for neurosurgical education based on interactive stereoscopic virtual reality (ISVR). Interactive stereoscopic virtual reality can be used to recreate the three-dimensional (3D) experience of neurosurgical approaches much more realistically than standard educational methods. The demonstration of complex 3D relationships is unrivaled and easily combined with interactive learning and multimedia capabilities.
Interactive stereoscopic virtual reality permits the accurate recreation of neurosurgical approaches through integration of several forms of stereoscopic multimedia (video, interactive anatomy, and computer-rendered animations). The content explored using ISVR is obtained through a combination of approach-based cadaver dissections, live surgical images and videos, and computer-rendered animations. These media are combined through an interactive software interface to demonstrate key aspects of a neurosurgical approach (for example, patient positioning, draping, incision, individual surgical steps, alternative steps, relevant anatomy). The ISVR platform is designed for use on a desktop personal computer with newly developed, inexpensive, platform-independent shutter glasses.
Interactive stereoscopic virtual reality has been used to capture the anatomy and methods of several neurosurgical approaches. In this paper the authors report their experience with ISVR and describe its potential advantages. The success of a neurosurgical approach is contingent on the mastery of complex, 3D anatomy. A new technology for neurosurgical education, ISVR can improve understanding and speed the learning process. It is an effective tool for neurosurgical education, bridging the substantial gap between textbooks and intraoperative training.
L. Fernando Gonzalez, Cameron G. McDougall, Felipe C. Albuquerque, Louis J. Kim and Robert F. Spetzler
The aim of this study was to assess the incidence, indications, complications, and angiography results associated with balloon-assisted coil embolization (BACE) of intracranial aneurysms and to compare these factors with those for conventional coil embolization (CE).
Between 1995 and 2005, 827 intracranial aneurysms in 757 consecutive patients were packed with coils. Balloon-assisted coil embolization was used in 8.6% (71 of 827) of the coil insertion procedures and was more frequently used in large aneurysms, un-ruptured lesions, and those located on the vertebrobasilar system and carotid artery. Procedure-related complications leading to death or dependency were significantly higher in BACEs (14.1%) compared with those in CEs (3%). Packing densities and the results of 6-month follow-up angiography studies did not differ significantly between the two types of treatments. There was a strong trend for a higher retreatment rate in the aneurysms treated with BACE.
Balloon-assisted coil embolization of intracranial aneurysms is associated with a high complication rate and should only be used if conventional CE of these lesions is impossible or has failed and if anticipated surgical risks are too high. The BACE procedure does not improve the occlusion rates of the aneurysms on follow-up evaluation.
Stephen J. Monteith, Asterios Tsimpas, Aaron S. Dumont, Stavropoula Tjoumakaris, L. Fernando Gonzalez, Robert H. Rosenwasser and Pascal Jabbour
Despite advances in surgical and endovascular techniques, fusiform aneurysms remain a therapeutic challenge. Introduction of flow-diverting stents has revolutionized the treatment of aneurysms with wide necks and of complex morphology. The authors report their experience with the endovascular treatment of fusiform aneurysms using the Pipeline Embolization Device.
A retrospective review of 146 patients with cerebral aneurysms treated with the Pipeline Embolization Device between June 2011 and January 2013 was performed. Twenty-four patients were identified as having fusiform aneurysms. Twenty-four aneurysms in these 24 patients were treated. The mean patient age was 59 years. There were 9 men and 15 women. Angiographic and clinical data (including the modified Rankin Scale [mRS] score) were recorded at the time of treatment and at follow-up. The aneurysms were located in the internal carotid artery in 8 patients (33.3%), middle cerebral artery in 8 patients (33.3%), anterior cerebral artery in 1 patient (4%), and vertebrobasilar circulation in 7 patients (29%). The aneurysms were smaller than 10 mm in 3 patients, 10–25 mm in 16 patients, and larger than 25 mm in 5 patients. The mean largest dimension diameter was 18 mm.
Stent deployment was successful in all cases. The minor procedural morbidity was 4% (1 case). Morbidity and mortality related to aneurysm treatment were 4.2% and 4.2%, respectively. The mean mRS scores preoperatively and at clinical follow-up (median 6.0 months, mean 6.9 months) were 0.71 and 1.2, respectively (91.7% presented with an mRS score of 2 or better, and 79.2% had an mRS score of 2 or better at the 6.0-month follow-up). At clinical follow-up, 82.6% of patients were stable or had improved, 13.0% worsened, and 4.2% had died. Twenty-two (91.7%) of 24 patients had follow-up angiography available (mean follow-up time 6.3 months); 59% had excellent angiographic results (> 95% or complete occlusion), 31.8% had complete aneurysm occlusion, 27.3% had greater than 95% aneurysm occlusion, 18.2% had a moderate decrease in size (50%–95%), 4.5% had a minimal decrease in size (< 50%), 13.6% had not changed, and 4.5% had an increase in size.
This series demonstrates that endovascular treatment of fusiform cerebral aneurysms with flow diversion was a safe and effective treatment. Procedural complications were low. Long-term morbidity and mortality rates were acceptable given the complex nature of these lesions.
Nohra Chalouhi, Pascal Jabbour, Robert M. Starke, Stavropoula I. Tjoumakaris, L. Fernando Gonzalez, Samantha Witte, Robert H. Rosenwasser and Aaron S. Dumont
Surgical clipping of posterior inferior cerebellar artery (PICA) aneurysms can be challenging and carries a potentially significant risk of morbidity and mortality. Experience with endovascular therapy has been limited to a few studies. The authors assess the feasibility, safety, and efficacy of endovascular therapy in the largest series of proximal and distal PICA aneurysms to date.
A total of 76 patients, 54 with proximal and 22 with distal PICA aneurysms, underwent endovascular treatment at Jefferson Hospital for Neuroscience between 2001 and 2011.
Endovascular treatment was successful in 52 patients (96.3%) with proximal aneurysms and 19 patients (86.4%) with distal aneurysms. Treatment consisted of selective aneurysm coiling in 60 patients (84.5%) (including 4 with stent assistance and 4 with balloon assistance) and parent vessel trapping in 11 patients (15.5%). Specifically, a deconstructive procedure was necessary in 9.6% of proximal aneurysms (5 of 52) and 31.6% of distal aneurysms (6 of 19). There were 9 overall procedural complications (12.7%), 6 infarcts (8.5%; 4 occurring after deliberate occlusion of the PICA), and 3 intraprocedural ruptures (4.2%). The rate of procedure-related permanent morbidity was 2.8%. Complete aneurysm occlusion was achieved in 63.4% of patients (45 of 71). One patient (1.4%) treated with selective aneurysm coiling suffered a rehemorrhage on postoperative Day 15. The mean angiographic follow-up time was 17.2 months. Recurrence and re-treatment rates were, respectively, 20% and 17.1% for proximal aneurysms compared with 30.8% and 23.1% for distal aneurysms. Favorable outcomes (moderate, mild, or no disability) at follow-up were seen in 93% of patients with unruptured aneurysms and in 78.7% of those with ruptured aneurysms.
Endovascular therapy is a feasible, safe, and effective treatment in patients with proximal and distal PICA aneurysms, providing excellent patient outcomes and adequate protection against rehemorrhage. The long-term incidence of aneurysm recanalization appears to be high, especially in distal aneurysms, and requires careful angiographic follow-up.
Kris A. Smith, Lynn S. Ashby, L. Fernando Gonzalez, David G. Brachman, Terry Thomas, Stephen W. Coons, Matthew Battaglia and Adrienne C. Scheck
The purpose of this study was to determine whether increased local control and improved survival can be achieved in patients with glioblastoma multiformes (GBMs) who undergo aggressive resection, Gliadel wafer implantation, Gamma Knife radiosurgery (GKS), and fractionated radiotherapy (RT) as the initial treatment.
Thirty patients with radiographically suspected GBMs were screened for enrollment in a Phase I/II prospective clinical trial. Twenty-seven patients were eligible and underwent gross-total resection and Gliadel wafer implantation. Gamma Knife radiosurgery (12 Gy at 50%) was administered to the resection cavity within 2 weeks of surgery. Patients then received standard fractionated RT (total dose 60 Gy over 6 weeks). Temozolomide was prescribed for patients at the time of recurrence. Surveillance MR imaging, neurological examination, and quality-of-life evaluations were performed at 2-month intervals. To estimate the potential effects on the DNA repair mechanism, tumor tissue was analyzed with methylation-specific polymerase chain reaction analysis and immunohistochemical assays for MGMT gene promoter methylation and protein expression.
The median survival for all patients was 50 weeks and the 2-year survival rate was 22%. When stratified into standard and high-risk patient groups, the median survivals were 76 and 33 weeks, respectively. Two patients remain alive at the time of this report with no clinical or radiographic evidence of disease at > 189 and 239 weeks posttreatment and excellent performance status. Local tumor control was achieved in 53% of patients, and local failure occurred in 47%. No acute early toxicity was noted; however, delayed symptomatic radionecrosis occurred in 47% of patients, which required repeated operations 9–24 months after the initial treatment. Delayed hydrocephalus requiring ventriculoperitoneal shunt placement occurred in 47% of patients. There was a significant difference in survival between patients whose tumors contained the methylated and unmethylated MGMT promoter, 103 versus 45 weeks, respectively (p = 0.0009, log-rank test).
The combination of aggressive resection, Gliadel wafer implantation, and GKS in addition to standard fractionated RT in selected patients resulted in increased local control and increased survival compared with a historical control group treated with surgery and involved-field RT alone. Delayed focal radionecrosis was increased to 47% in this series and was managed with steroids and repeated resection. Aggressive local tumor control with these multimodal therapies should be approached judiciously for a select group of high performance patients and the probability of developing symptomatic radionecrosis requiring surgery should be anticipated and fully disclosed to patients who undergo this treatment.
Ana Rodríguez-Hernández, Ahmed J. Awad and Michael T. Lawton
Nohra Chalouhi, Cory D. Bovenzi, Vismay Thakkar, Jeremy Dressler, Pascal Jabbour, Robert M. Starke, Sonia Teufack, L. Fernando Gonzalez, Richard Dalyai, Aaron S. Dumont, Robert Rosenwasser and Stavropoula Tjoumakaris
Aneurysm recurrence after coil therapy remains a major shortcoming in the endovascular management of cerebral aneurysms. The need for long-term imaging follow-up was recently investigated. This study assessed the diagnostic yield of long-term digital subtraction angiography (DSA) follow-up and determined predictors of delayed aneurysm recurrence and retreatment.
Inclusion criteria were as follows: 1) available short-term and long-term (> 36 months) follow-up DSA images, and 2) no or only minor aneurysm recurrence (not requiring further intervention, i.e., < 20%) documented on short-term follow-up DSA images.
Of 209 patients included in the study, 88 (42%) presented with subarachnoid hemorrhage. On shortterm follow-up DSA images, 158 (75%) aneurysms showed no recurrence, and 51 (25%) showed minor recurrence (< 20%, not retreated). On long-term follow-up DSA images, 124 (59%) aneurysms showed no recurrence, and 85 (41%) aneurysms showed recurrence, of which 55 (26%) required retreatment. In multivariate analysis, the predictors of recurrence on long-term follow-up DSA images were as follows: 1) larger aneurysm size (p = 0.001), 2) male sex (p = 0.006), 3) conventional coil therapy (p = 0.05), 4) aneurysm location (p = 0.01), and 5) a minor recurrence on short-term follow-up DSA images (p = 0.007). Ruptured aneurysm status was not a predictive factor. The sensitivity of short-term follow-up DSA studies was only 40.0% for detecting delayed aneurysm recurrence and 45.5% for detecting delayed recurrence requiring further treatment.
The results of this study highlight the importance of long-term angiographic follow-up after coil therapy for ruptured and unruptured intracranial aneurysms. Predictors of delayed recurrence and retreatment include large aneurysms, recurrence on short-term follow-up DSA images (even minor), male sex, and conventional coil therapy.