J Neurosurg 77:501-507, 1992 Special Article Direct thrombosis of aneurysms with cellulose acetate polymer Part II: Preliminary clinical experience KAZUSHI KINUGASA, M.D., SltlNYA MANDAI, M.D., YOSHINORI TERAI, M.D., ICHIRO KAMATA, M.D., KENJI SUGIU, M.D., TAKASHI OHMOTO, M.D., AND AKIRA NISHIMOTO, M.D. Department ~?fNeurological Surgery. Okayama University Medical School, Okayama. Japan ~" The authors report the treatment of seven intracranial aneurysms in six patients with direct infusion of cellulose acetate polymer solution, a new liquid thrombotic material. These aneurysms were considered inoperable because of their size or location, or because of the patient's neurological condition. This material avoids the difficulties associated with balloon occlusion, and completely fills even irregularly shaped aneurysms. Cellulose acetate polymer solution hardens in about 5 minutes and remains solid once inside the aneurysm. Because this technique is less invasive than surgery, it can be used for high-risk patients in the acute stage of subarachnoid hemorrhage. Transient motor aphasia occurred in one patient. A small residual neck, which caused rebleeding 3 months after the treatment, remained in another patient. This article describes the new material, the procedure for direct thrombosis, and preliminary clinical results. KEY WORDS 9 aneurysm . thrombotic material 9 endovascular technique cellulose acetate polymer ' interventional neuroradiology N 1974, Serbinenko 19 reported the successful treatment of carotid aneurysms in 82 patients by occlusion of the aneurysm with a detachable balloon. Since then, balloon thrombosis has proved to be an effective treatment for aneurysms that are difficult to reach surgically. For aneurysms with a broad or unapparent neck and those located in the cavernous portion of the carotid artery, the parent artery was occluded across the aneurysm but just proximal to it. This was done through ligation of the internal carotid artery (ICA) or occlusion with endovascular detachable balloons) '6"7 With recent developments in microballoon techniques, it is now possible to enter the aneurysm directly and occlude it with a balloon while preserving the parent artery. 8-~2 Balloon embolization, however, cannot easily occlude the entire aneurysmal sac along with the bleb. Although rare, some reports describe the enlargement or rupture of the aneurysm, the distal propulsion of the balloon, and migration of the thrombus from the neck of the aneurysm after incomplete occlusion.~32~ These I J. Neurosurg. / Volume 77/October, 1992 9 factors have led us to believe that filling the inside of the aneurysm directly with a liquid material that solidifies would be better than balloon embolization. This technique uses a liquid thrombotic material, cellulose acetate polymer. Part I of this study ~5 reports the experimental and histochemical results of this treatment. Here, we describe the clinical application of this thrombotic material. Clinical Material and Methods Patient Population Six patients diagnosed as having intracranial aneurysms or subarachnoid hemorrhage (SAH) were admitted to our hospital over a 5-month period. The average age of these patients was 50 years (range 29 to 64 years); the female to male ratio was 1:1. Endovascular treatment using cellulose acetate polymer was considered suitable for seven o f the eight aneurysms found in these patients. Overall, we employed the thrombotic procedure eight times; thrombosis was repeated in one patient 501 K. Kinugasa, el al. F~r 1. Case 1. A: Left carotid angiogram, lateral projection, showing a ruptured internal carotid artery (1CA)-ophthalmic artery ancurysm measuring 8 x 11 ram, arising from the carotid artery. B: Angiogram obtained through a Tracker-18 catheter, lateral projection, showing a small amount of contrast medium along the posterior wall of the aneurysm. A faint retrograde flow of contrast material (arrows) is seen in the proximal ICA. C: Post-thrombotic angiogram showing the lumen of the aneurysm occluded with cellulose acetate polymer. A small crescent of residual neck (arrow) can be seen in the anterior portion of the aneurysmal sac. D: Left carotid artery angiogram showing grouah of the residual neck (arron'). E: Angiogram showing complete obliteration of the aneu~sm with preservation of the parent arte~'. (Case, 1) because of bleeding from the residual neck of an ICA-ophthalmic artery aneurysm. One aneurysm occurred in the ICA-ophthalmic artery, one in the ICAposterior communicating artery (PCoA), one in the intracavernous portion of the ICA, one in the basilar artery (BA)-superior cerebellar artery (SCA), and three in the bifurcation of the BA. An unruptured aneurysm of the anterior communicating artery (ACoA) was clipped in one patient (Case 2). Indications for Treatment Indications for treatment with cellulose acetate polymer included: 1) prior surgical procedures that failed to clip the neck of the aneurysm; 2) locations difficult to reach surgically, such as the cavernous segment of the ICA; 3) the patient's inability to tolerate general anesthesia; and 4) excessive risk in surgical clipping of the aneurysm because of its size or location or because of the patient's neurological status. Consequently, this series favored a high-risk group of patients in whom standard neurosurgical treatment failed or who were poor candidates for surgery. All patients or a member of the family gave their informed consent before treatment began. Occlusion Technique All procedures were performed in the interventional neuroangiography suite using high-resolution digital subtraction angiography, the road-mapping technique, and rapid-sequence filming. Cellulose acetate polymer thrombosis was performed under local anesthesia via bilateral transfemoral approaches, and the patients were awake throughout the procedure. A No. 8 French sheath was placed into each femoral artery, and a No. 6.5 French tapered catheter was inserted through each femoral sheath. A four-vessel cerebral angiogram was obtained to assess the size and shape of the aneurysm, route of access, the relationship 502 of the aneurysmal neck to the parent vessel, and the collateral blood flow. During occlusion of aneurysms in the anterior circulation, angiography was performed through one catheter and a Tracker-18 infusion catheter* was inserted into the other catheter. The tip of the Tracker-18 catheter was gently guided into the aneurysm and precisely positioned at the deepest part of the sac. For aneurysms in locations unfavorable to navigation via the parent vessel, a Tracker-18 catheter can be steam-formed into an appropriate shape and used in conjunction with a 0.014-in. steerable guide wire to help place its tip directly in the aneurysm. To prevent cellulose acetate polymer from washing into the distal artery through the neck of the aneurysm, the carotid arteff was compressed using Matas' method to reduce the main circulation to the aneurysm. ~9Because Matas' method effectively reduces blood flow, a part of the contrast material injected into the aneurysm via the Tracker-18 catheter remains inside the aneurysm. For aneurysms in the posterior circulation, a No. 8 French nontapered guiding catheter was placed into the proximal vertebral artery. The microballoon catheter was then advanced through the guiding catheter into the midportion of the BA. This method was used in place of Matas' method to reduce blood flow. The other No. 6.5 French tapered catheter, including the Tracker-18 catheter, was placed into the opposite proximal vertebral artery. The tip of the Tracker- 18 catheter was then gently guided into the sac of the aneurysm. Dimethyl sulfoxide (DMSO) (0.37 ml) was injected to irrigate the lumen of the catheter. The DMSO was then replaced with cellulose acetate polymer prepared as described in Part I of this study. ~5 Cellulose acetate polymer was infused slowly over a period of 3 to 5 minutes until the lumen of the aneurysm was imper* Tracker-18 infusion catheter manufactured by Target Therapeutics, San Jose, California. J. Neurosurg. / Volume 77/October, 1992 T h r o m b o s i s w i t h c e l l u l o s e a c e t a t e p o l y m e r in p a t i e n t s Fla. 2. Case 2. A: Left internal carotid artery angiogram, lateral projection, demonstrating an irregularly shaped aneurysm originating from the internal carotid artery (ICA), and an unruptured aneurysm of the anterior communicating artery (arrow). The tip of the catheter is in the sac of the ruptured aneurysm. B: Angiogram after injection of cellulose acetate polymer into the aneu~sm. The aneurism is totally occluded; normal filling of the ICA and posterior communicating artery remains. C: Angiogram taken 6 months after the procedure. The aneurism is still obliterated by cellulose acetate polymer. D: Skull x-ray film demonstrating the solidified polymer within the aneurysmal sac. The sac retains the same size and configuration it had immediately after injection of the thrombotic material. ceptible under direct fluoroscopic visualization. Contrast material was injected through the No. 8 French guiding catheter or the No. 6.5 French tapered catheter to confirm the degree of polymer thrombosis. After the carotid artery was decompressed or the microbailoon deflated, angiography revealed a small crescent-shaped residual neck. To fill this space, small amounts of cellulose acetate polymer were introduced in the same way. We verified that this material had completely occluded the sac of the aneurysm and that the blood flow of the parent artery, had been satisfactorily preserved. The catheter was then withdrawn smoothly and without resistance because cellulose acetate polymer is not adhesive. A final angiogram was obtained to check the occlusion and patency of the parent vessel. We did not use heparin in any patient because of the timing of the procedure following aneurysmal rupture. Case Reports Case 1 This 61-year-old right-handed man suddenly lost consciousness on February 25, 1991. At admission, he was semicomatose and unresponsive to commands. Cerebral angiography demonstrated an ICA-ophthalmic artery aneurysm measuring 8 x 11 ram, originating from the dorsal wall of the left ICA (Fig. 1A). Computerized tomography revealed mild hydrocephalus and dilated ventricles. A continuous spinal drainage tube was inserted into the subarachnoid space of the lumbar region. Operation. We treated the aneurysm using cellulose acetate polymer and a Tracker-18 catheter 17 hours after the onset of SAH. The tip of the catheter was carefully introduced into the sac of the aneurysm. Matas' method was used to compress the left carotid artery. During compression, a small amount of contrast maJ. Neurosurg. / Volume 77/October. 1992 terial injected through the catheter remained in the lumen of the aneurysm, and a faint retrograde flow of contrast medium was observed in the proximal ICA (Fig. I B). Cellulose acetate polymer (0.47 ml) was slowly injected into the aneurysmal sac. On the angiogram obtained after treatment, a small crescent of contrast medium lying along the anterior portion of the lumen of the aneurysm was visible during the early arterial phase (Fig. 1C). Postoperative Course. After treatment, the patient showed no neurological change but gradually recovered consciousness over the next several weeks. An angiogram obtained 5 weeks after thrombosis showed that the size of the residual neck and cellulose acetate polymer had not changed. On May 31, the patient suddenly sustained another SAH. An angiogram demonstrated a growing crescent of residual neck measuring 2.5 x 12 m m (Fig. ID). Through a transfemoral route, a Tracker-18 catheter was directed into the aneurysm and 0.14 ml cellulose acetate polymer was slowly infused into the sac of the aneurysm. After treatment, angiography demonstrated that the aneurysm was obliterated and the parent vessel was preserved (Fig. I E). A follow-up angiogram 5 months after the procedure showed continued obliteration of the aneurysm and normal filling of the intracranial circulation. At 8 months after the procedure, the patient is neurologically intact except for a mild gait disturbance. Case 2 This 42-year-old woman came for medical evaluation of confusion, severe headache, right hemiparesis, and a stiff neck on March 15, 1991. Cerebral angiography demonstrated rupture of a left |CA-PCoA aneurysm, measuring 9 x 11 mm, as well as an unruptured aneurysm in the ACoA (Fig. 2A). 5013 K. Kinugasa, et al. filled with 0.03 ml contrast material and inflated to preserve the PCA; 6.0 ml cellulose acetate polymer was infused into the sac of the aneurysm through the Tracker- 18 catheter. Postoperative Course. An angiogram obtained immediately after treatment showed that the basilar bifurcation aneurysm was obliterated and the PCA was preserved. Faint contrast material was seen around the cellulose acetate polymer (Fig. 4C). The patient was in stable neurological condition during this procedure. An angiogram 1 month after the procedure showed that the area of faint contrast material had disappeared, and another at 5 months after treatment proved that the PCA was preserved (Fig. 4D). FIG. 3. Case 2. Operative photograph during craniotomy for an unruptured aneurysm (AN) of the anterior communicating artery. The aneurysmal sac contains black thrombosis and white cellulose acetate polymer. ICA = internal carotid artery. Operation. A Tracker- 18 catheter was immediately inserted into the ruptured ICA-PCoA aneurysm. The aneurysm had a cloverleaf configuration, and 0.275 ml cellulose acetate polymer was injected using Matas' procedure under fluoroscopy. Injection was continued slowly until the polymer completely filled the aneurysm, preserving the ICA (Fig. 2B). Four days later, the ACoA aneurysm was surgically clipped. During the clipping of this aneurysm, the surface of the sac of the first aneurysm was exposed, revealing a small black thrombus and the white cellulose acetate polymer within the aneurysmal sac (Fig. 3). Postoperative Course. Six months later, a followup arteriogram showed complete clipping of the ACoA aneurysm and continued total occlusion of the ICAPCoA aneurysm with cellulose acetate polymer (Fig. 2C). A plain skull x-ray film showed the polymer to be the same size as it had been at the time of thrombosis (Fig. 2D). After thrombosis, the patient's neurological deficit gradually improved, but she had mild right hemiparesis. Case 4 This 29-year-old man suffered from gradually increasing weakness of his extremities and dysarthria. Vertebral angiography showed a giant aneurysm containing a thrombus at the basilar bifurcation (Fig. 4A). The left posterior cerebral artery (PCA) emerged from the sac of the aneurysm; thus, complete obliteration of the sac of the aneurysm would also occlude the proximal PCA. Operation. We used a Tracker-18 catheter to infuse cellulose acetate polymer and a microballoon catheter to preserve the parent artery. These catheters were directed up the posterior circulation, through the BA, and into the aneurysm (Fig. 4B). The microballoon was 504 Case 5 This 53-year-old man presented with SAH and severe headache. His neurological condition was classified as Grade III according to the scale of Hunt and Kosnik.~4 A cerebral angiogram showed aneurysms at the basilar bifurcation and the BA-SCA (Fig. 5A). Surgical exploration had been unsuccessful because of the location of the aneurysms and the acute effects of the hemorrhage, and the aneurysms were considered inoperable. The patient suddenly lost consciousness 21 days after SAH. Operation. Emergency endovascular occlusion of the aneurysms using cellulose acetate polymer was performed. A Tracker-18 catheter was gently advanced into the basilar bifurcation aneurysm. The BA was catheterized with a nondetachable microballoon catheter to reduce the blood flow of the parent artery, and cellulose acetate polymer was infused into the sacs of both the basilar aneurysm (0.58 ml) and the BA-SCA aneurysm (0.47 ml). The basilar bifurcation aneurysm was completely thrombosed (Fig. 5B), but the BA-SCA aneurysm was incompletely thrombosed to preserve both the PCA and the SCA originating from the dome of the aneurysm (Fig. 5C). Postoperative Course. An angiogram obtained immediately after the treatment showed complete occlusion of the basilar bifurcation aneurysm and about 90% occlusion of the BA-SCA aneurysm. The patient was neurologically unchanged during this procedure. Six days after treatment, he died as a result of primary brain damage caused by the two episodes of SAH. Results Table 1 summarizes the complications, follow-up results, and outcomes in this series of seven aneurysms in six patients. All aneurysms were thrombosed to a degree ranging from 80% to 100% using cellulose acetate polymer. Occlusion was incomplete in some aneurysms to preserve the normal vessel originating from the aneurysm. Complications associated directly with treatment occurred in two patients (Cases 1 and 3). Case 1 is reported fully above. In Case 3, the intracavernous aneurysm was ectatic without a well-defined neck. Test occlusion of the proximal cervical ICA was J. Neurosurg. / Volume 77/October, 1992 Thrombosis with cellulose acetate polymer in patients FIG. 4. Case 4. A: Vertebral angiogram demonstrating a large aneurysm at the basilar bifurcation. B: Diagram illustrating the tip of the Tracker-18 catheter as it is positioned in the dome of the aneurysm. A microballoon catheter is located in the neck of the aneurvsm to preserve the posterior cerebral artery (PCA). SCA = superior cerebellar artery. C: Angiogram obtained after the procedure showing obliteration of the dome of the aneurysm. The proximal sac (arrow) has been maintained to preserve the origin of the PCA. D: Conventional subtraction angiogram obtained 5 months after the procedure showing the PCA still preserved. The opacified irregular mass representing cellulose acetate polymer (ctrrows)can be clearly seen. well tolerated for 30 minutes, and the patient developed no focal neurological problems. Therefore, the carotid artery was occluded with cellulose acetate polymer infused into the ICA just proximal to the neck of the aneurysm, as well as into the aneurysmal dome. The contralateral carotid angiogram obtained after the thrombotic procedure showed enough blood supply in the ipsilateral hemisphere. The presenting symptom was considered to be correlated with the hemodynamic change after the treatment. After the procedure, the patient developed mild motor aphasia, which resolved in 5 days. No permanent neurological deficits occurred in this series. The single death (Case 5) was due to primary brain damage caused by two episodes of SAH. Discussion Cellulose acetate polymer is widely employed as a component of membranes contained in renal dialyzers. ~8Dimethyl sulfoxide has been used to reduce intra- FIG. 5. Case 5. A: Vertebral angiogram, anteroposterior view, demonstrating a basilar artery (BA) bifurcation and a BA-superior cerebellar artery (SCA) aneurysm. The tip of the catheter (arrowhead) is seen in the dome of the aneurysm. A partially inflated balloon (arrow) was temporarily placed in the mid-basilar artery to reduce blood flow. B: Angiogram obtained after thrombosis of the basilar bifurcation aneurysm showing that the aneurysm is obliterated. Cellulose acetate polymer impinges slightly on the proximal posterior cerebral artery (PCA). C: Angiogram obtained after thrombosis of the BA-SCA aneurysm. Thrombosis is incomplete to preserve the SCA and PCA. The tip of the catheter (arrowhead) is seen in the aneurysm. A balloon (arrow) is placed at the origin of the aneurysm. J. Neurosurg. / Volume 77 / October, 1992 505 K . K i n u g a s a , el al. TABLE 1 (Tmical summafT ol~i.v pa:iem.~ ttec:ted with