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Ichiro Yuki, Yuichi Murayama and Fernando Viñuela

Object. The authors report on a series of 29 patients presenting with acute subarachnoid hemorrhage (SAH) related to the rupture of a vertebrobasilar dissecting aneurysm. Special attention was focused on embolization techniques and immediate and midterm anatomical and clinical outcomes.

Methods. Between March 1994 and January 2003, 29 patients presented with acute SAH caused by the rupture of a vertebrobasilar dissecting aneurysm. Eleven patients (37.9%) had Hunt and Hess Grade I SAH, four (13.8%) Grade II, six (20.7%) Grade III, five (17.2%) Grade IV, and three (10.3%) Grade V. Aneurysms were classified into five groups based on lesion location, and treatment courses were decided. All patients except two were treated by endovascular trapping of the aneurysm with concomitant occlusion of the involved vertebral artery (VA). No technical or clinical complication was observed in 28 patients (97%). Aneurysm perforation occurred during the procedure in one patient (3%). There was evidence of aneurysm recanalization in one patient. One patient with Hunt and Hess Grade IV SAH and two patients with Grade V SAH died. One patient died of respiratory infection 1 year after aneurysm trapping. One patient presented with a recurrent hemorrhage 1 month after treatment and died. Overall morbidity and mortality rates were 13.8 and 17.2%, respectively.

Conclusions. Twenty-nine patients with acute SAH due to rupturing of vertebrobasilar dissecting aneurysms were treated using endovascular techniques. In most cases, endovascular trapping of the aneurysm and concomitant occlusion of the VA was technically and clinically successful.

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Yuichi Murayama, Fernando Viñuela, Akira Ishii, Yih-Lin Nien, Ichiro Yuki, Gary Duckwiler and Reza Jahan

Object

The Matrix detachable coil is a new bioactive, bioabsorbable coil used in the endovascular embolization of intracranial aneurysms. It has a platinum core covered with a bioactive, bioabsorbable polymer (polyglycolic acid/lactide). The authors report on their initial midterm clinical experience with the first-generation Matrix detachable coil.

Methods

One hundred twelve patients harboring 118 aneurysms were treated using Matrix coils. Forty-nine aneurysms (41.5%) were associated with acute subarachnoid hemorrhage (SAH). Twenty-four lesions (49%) were harbored by patients with Hunt and Hess Grade I, 11 (23.4%) by patients with Grade II, eight (16.3%) by those with Grade III, and six (12.2%) by those with Grade IV. Four aneurysms (3.4%) were harbored by patients who had presented with nonacute SAH. Sixty-five aneurysms (55%) were unruptured. Fifty-seven lesions (48.3%) were small with a small neck, 29 (24.6%) were small with a wide neck, 30 (25.4%) were large, and two (1.7%) were giant. All patients were followed up to obtain angiography and clinical outcome data.

Technical complications occurred in six patients: two thromboembolic complications and four aneurysm perforations. Of these six patients, the status of two deteriorated because of aneurysm perforation and another two because of thrombus formation (morbidity 3.6%). There were five deaths—one due to rerupture after embolization. Angiography follow-up studies of 87 aneurysms were obtained. Seventy aneurysms demonstrated progressive occlusion or a stable neck (80.5%), and 17 had some degree of recanalization (19.5%). The aneurysms originally diagnosed as a neck remnant showed a 15% rate of recanalization.

Conclusions

Matrix coils can be delivered into aneurysms with technical complications similar to those encountered using GDCs. Midterm anatomical outcomes to date have shown moderate improvement in the recanalization rate when compared with those realized using the GDC system. Because of the increased friction associated with the first-generation Matrix coil, the packing density in most aneurysms was less than that achieved with GDCs. Prolonged angiography follow-up evaluations are needed to document long-term efficacy.

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Ichiro Yuki, Daniel Lee, Yuichi Murayama, Alexander Chiang, Harry V. Vinters, Ichiro Nishimura, Chiachien J. Wang, Akira Ishii, Benjamin M. Wu and Fernando Viñuela

Object

Bioabsorbable polymeric material coils are being used in the endovascular treatment of aneurysms to achieve better thrombus organization than is possible using bare platinum coils. We used immunohistochemical and molecular biological analysis techniques in experimental aneurysms implanted with three different bioabsorbable polymer coils and platinum coils.

Methods

The degradation kinetics of nine polymer candidates for further analysis were first analyzed in vitro, and three materials with different degradation rates were selected. Seventy-four aneurysms were created in 37 swine using the venous pouch technique. The aneurysms were surgically implanted with one of the materials as follows (time points = 3, 7, and 14 days): Group 1, Guglielmi detachable coils (platinum); Group 2, Polysorb (90:10 polyglycolic acid [PGA]/polylactic acid); Group 3, Maxon (PGA/trimethylene carbonate); and Group 4, poly-l-lactic acid. Histological, immunohistochemical, and cDNA microarray analyses were performed on tissue specimens.

Results

Groups 1 and 4 showed minimal inflammatory response adjacent to the coil mass. In Group 2, Polysorb elicited a unique, firm granulation tissue that accelerated intraaneurysmal thrombus organization. In Group 3 intermediate inflammatory reactions were seen. Microarray analysis with Expression Analysis Sytematic Explorer software showed functional-cluster-gene activation to be increased at Day 7, preceding the histologic manifestation of polymer-induced granulation tissue at Day 14. A profile of expression changes in cytokine-related and extracellular membrane–related genes was compiled.

Conclusions

Degradation speed was not the only factor determining the strength of the biological response. Polysorb induced an early, unique granulation tissue that conferred greater mechanical strength to the intraaneurysmal coil–thrombus complex. Enhancing the formation of this polymer-induced granulation tissue may provide a new direction for improving long-term anatomical outcomes in cases involving aneurysms embolized with detachable coils.

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Daniel Lee, Ichiro Yuki, Yuichi Murayama, Alexander Chiang, Ichiro Nishimura, Harry V. Vinters, Chiachien J. Wang, Yih-Lin Nien, Akira Ishii, Benjamin M. WU and Fernando Viñuela

Object

The authors describe the process of thrombus organization in the swine surgical aneurysm model.

Methods

Lateral carotid artery aneurysms with immediately induced thrombosis were created in 31 swine for a time-course study. Aneurysms were evaluated at 1, 3, 7, 14, 30, and 90 days after they were created. Histological analyses included quantitative immunohistochemical studies and evaluation of collagen deposition. Complementary DNA microarray analysis was performed for gene expression profiling. The lists of up- and downregulated genes were cross-matched with lists of genes known to be associated with cytokines or the extracellular matrix. The expression of selected genes was quantified using real-time polymerase chain reaction. Functional clustering was performed with the Expression Analysis Systematic Explorer (EASE) bioinformatics package.

Results

Histological analysis demonstrated leukocyte and macrophage infiltration in the thrombus at Day 3, myofibroblast infiltration at Days 7 to 14, and progressive collagen deposition and contraction thereafter. Tissue organization occurred in a centripetal fashion. A previously undescribed reticular network of connective tissue was observed at the periphery of the aneurysm at Day 3. Macrophages appeared critical to this thrombus organization. A total of 1109 genes were significantly changed from reference time zero during the time course: CXCL14, which produces a monocyte-specific chemokine, was upregulated over 100-fold throughout the time course; IGF1 was upregulated fourfold at Day 7, whereas IGFBP2 was downregulated approximately 50% at Days 7 and 14. Osteopontin (SPP1) upregulation increased from 30-fold at Day 30 to 45-fold at Day 14. The EASE analysis yielded eight functional classes of gene expression.

Conclusions

This investigation provides a detailed histological and molecular analysis of thrombus organization in the swine aneurysm model. The companion study will describe the effect of embolic bioabsorbable polymers on this process.

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Ichiro Yuki, Robert H. Kim, Gary Duckwiler, Reza Jahan, Satoshi Tateshima, Nestor Gonzalez, Alessandra Gorgulho, Jorge Lee Diaz, Antonio A. De Salles and Fernando Viñuela

Object

High-flow fistulas associated with brain arteriovenous malformations (AVMs) pose a significant challenge to both stereotactic radiosurgery (SRS) and surgical treatment. The purpose of this study was to examine the outcomes of multimodality treatment of AVMs in association with a large arteriovenous fistula (AVF), with a special focus on endovascular embolization and its associated complications.

Methods

One hundred ninety-two patients harboring cerebral AVMs underwent endovascular treatment in the authors' department between 1997 and 2003. Of these, the authors selected 74 patients presenting with an AVM associated with high-flow AVF(s) for a retrospective analysis based on the findings of superselective angiography. After endovascular embolization, 32 patients underwent resection, 33 underwent either SRS or hypofractionated stereotactic radiotherapy (HSRT), and 3 underwent both surgery and SRS. Six patients underwent embolization only. Immediate and midterm treatment outcomes were analyzed.

Results

Fifty-seven (77%) of the 74 patients had AVMs that were Spetzler-Martin Grade III or higher. A complete resection was achieved in all 32 patients. Of patients who underwent SRS/HSRT, 13 patients (39.3%) had either complete or > 90% obliteration of the AVM, and 2 patients (6.1%) had incomplete obliteration. Fourteen patients (42.4%) with residual AVM underwent repeated radiotherapy (and remain under observation). Of the 3 patients who underwent both SRS and resection, resection was complete in 2 and incomplete in one. No follow-up was obtained in 6 patients (8.1%). An endovascular complication was observed in 4 patients (5.4%). Fistula embolization was safely performed in every patient, whereas every endovascular complication was associated with other procedures such as nidus embolization.

Conclusions

Endovascular occlusion of the fistulous component was successfully achieved in every patient; every endovascular complication in this series was related to other procedures such as nidus embolization. The importance of the fistula treatment should be emphasized to minimize the endovascular complications and to maximize the treatment effect when a multimodality therapy is used to treat brain AVMs with large AVF.

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Kazuyoshi Nakanishi, Nobuhiro Tanaka, Naosuke Kamei, Toshio Nakamae, Bun-ichiro Izumi, Ryo Ohta, Yuki Fujioka and Mitsuo Ochi

Object

The pathophysiology of occult tethered cord syndrome (OTCS) with no anatomical evidence of a caudally shifted conus and a normal terminal filum is hard to understand. Therefore, the diagnosis of OTCS is often difficult. The authors hypothesized that the posterior displacement of the terminal filum may become prominent in patients with OCTS who are in a prone position if filum inelasticity exists, and they investigated prone-position MRI findings.

Methods

Fourteen patients with OTCS and 12 control individuals were examined using T2-weighted axial MRI with the patients in a prone position on a flat table. On each axial view, the distance between the posterior and anterior ends of the subarachnoid space (A), the distance between the posterior end of the subarachnoid space and the terminal filum (B), the distance between the posterior end of the subarachnoid space and the dorsal-most nerve among the cauda equina (C), and the distance between the posterior end of the subarachnoid space and the ventral-most nerve (D) were measured. The location ratios of the terminal filum, the dorsal-most nerve, and the ventral-most nerve were calculated by the ratio of A to B (defined as TF = B/A), A to C (defined as DN = C/A), and A to D (defined as VN = D/A), respectively. Patients underwent sectioning of the terminal filum with the aid of a surgical microscope. The low-back pain Japanese Orthopaedic Association score was obtained before surgery and at the final follow-up visit.

Results

On prone-position axial MRI, the terminal filum was separated from the cauda equina and was shifted caudally to posterior in the subarachnoid space in all patients with OTCS. The locations of the caudal cauda equina shifted to ventral in the subarachnoid space. The TF values in the OTCS group were significantly lower than those in the control group at the L3–4 (p = 0.023), L-4 (p = 0.030), L4–5 (p = 0.002), and L-5 (p < 0.001) levels. In contrast, the DN values in the OTCS group were significantly higher than those of the control group at the L-2 (p = 0.003), L2–3 (p = 0.002), L-3 (p < 0.001), L3–4 (p < 0.001), L-4 (p = 0.007), L4–5 (p = 0.003), and S-1 (p = 0.014) levels, and the VN values in the OTCS group were also significantly higher than those of the control group at the L2–3 (p = 0.022), L-3 (p = 0.027), L3–4 (p = 0.002), L-4 (p = 0.011), L4–5 (p = 0.019), and L5–S1 (p = 0.040) levels. Sections were collected during surgery for histological evaluation, and a decreased elasticity within the terminal filum was suggested. Improvements in the Japanese Orthopaedic Association score were observed at the final follow-up in all patients.

Conclusions

The authors' new method of using the prone position for MRI shows that the terminal filum is located significantly posterior and the cauda equina is located anterior in patients with OTCS, suggesting a difference in elasticity between the terminal filum and cauda equina.