J Neurosurg 75:8-14, 1991 Special Article Electrothrombosis of saccular aneurysms via endovascular approach Part 2: Preliminary clinical experience GuIpo GUGLIELMI, M.D., FERNANDO VINUELA, M.D., JACQUES Dion, M.D., AND Gary DuCKWILER, M.D. Department of Neurological Sciences, Therapeutic Neuroangiography, University of Rome Medical School, Rome, ltaly; and Department of Radiological Sciences, Endovascular Therapy, University of California Medical Center, Los Angeles, California v Fifteen patients with high-risk intracranial saccular aneurysms were treated using electrolytically detachable coils introduced via an endovascular approach. The patients ranged in age from 21 to 69 years. The most frequent clinical presentation was subarachnoid hemorrhage (eight cases). Considerable thrombosis of the aneurysm (70% to 100%) was achieved in all 15 patients, and preservation of the parent artery was obtained in 14. Although temporary neurological deterioration due to the technique was recorded in one patient, no permanent neurological deficit was observed in this series and there were no deaths. It is believed that this new technology is a viable alternative in the management of patients with high-risk intracranial saccular aneurysms. It may also play an important role in the occlusion of aneurysms in the acute phase of subarachnoid hemorrhage. Key Worps + aneurysm + electrothrombosis + detachable coils + embolization - interventional neuroradiology + endovascular therapy Cooperative Study on the Timing of Aneurysm Surgery°® indicate that there is considerable room for improvement in the treatment of this disease. The technique of intra-aneurysmal electrothrombosis via an endovascular approach has been conceived in an attempt to improve the therapeutic management of patients harboring intracranial aneurysms. This tech- nique, the basic electrochemical principles on which it is based, and the results of the preclinical animal ex- perimentation are described in Part 1.' An evaluation of the preliminary clinical experience is reported here. T: recently published results of the International Clinical Material and Methods Patient Population Between March and November, 1990, high-risk sac- cular aneurysms in 15 patients were thrombosed via an endovascular approach with platinum detachable coils and intra-aneurysmal electrothrombosis (Table 1). In three cases the aneurysm was considered inoperable because of the presence of normal arteries arising from 8 or adherent to the sac of the aneurysm; two of these patients had undergone unsuccessful surgical explora- tion. In three other cases the aneurysm had been partially clipped or wrapped. In two further cases a myocardial infarct, concomitant with subarachnoid hemorrhage (SAH), contraindicated surgery. In five cases the aneurysm was judged inoperable because of its location. The aneurysm in the remaining two was explored and found unclippable. Ten patients were women and five were men. The patients ranged in age from 21 to 69 years (mean 49 years). Eight patients presented with SAH, five patients with mass effect, one with carotid-cavernous fistula due to rupture of an intracavernous aneurysm, and one with a large intracavernous pseudoaneurysm after bal- loon embolization of a carotid-cavernous fistula. All patients presenting with SAH were in good neurological condition (Grade I or II according to Hunt and Hess’ classification‘). Three aneurysms were intracavernous and five in- volved the basilar bifurcation. The remaining seven aneurysms involved one or more of the following: the J. Neurosurg. / Volume 75 / July, 1991 Part 2 Endovascular electrothrombosis of saccular aneurysms: “WOOL JO UoIsNjI50 WOOT[eq ‘oI9]dWOsU! UdAyap [109 yey £ Jeaqauao appl = VOW :Asaye SuTestuNUIWOS JOLIAIUL = YOY ‘uoNSuNS IRISeQorqayi9a = UONOUN! g A ‘ArOLTE [eIQeIA2 JOUAaIUe = YOV ‘Maur proses peusayu! = YI Auaue seljaqasaa soadns = VOS8 ‘ray [eiqaiaa 1oUaysod = Wd :Alaue sepJoqos199 JOLIAJUT IOINISOd = Wid :BeyLOWsY prlouyoregns = HYS :AIOWOUT IE[NOTO = “WOW “LINISY sNOULaATO-proIw) = LINISY DOD « “WW $7 < squRTs SW Cz 0} Z] :991B] tu Z] > ypeUg f “AIQUR “WAU UNUU-¢ “UID CT J uoOnROITYyIG poo YoIsn}s20 %001 06/6/11 auou —96/S/[ | “waW WU-g “Hd Op T poyey duane snoraad = jews sETISEG HVS ‘LS $1 pasoquiosyt 25 mm). Occlusion Technique All procedures are performed with the patient awake and under systemic heparinization. The transfemoral approach and digital subtraction angiography with “road-mapping” capability were used in all cases. The proximal parent artery (internal carotid or vertebral ar- tery) was catheterized with a No. 6 French nontapered polyethylene guiding catheter. A Tracker microcatheter was advanced coaxially into the aneurysm sac with the aid of a micro-guidewire.* The guidewire was removed once the microcatheter tip was inside the aneurysm sac in order to avoid aneurysm perforation. Continuous pressurized flushing of the coaxial system was utilized to decrease friction and eliminate the possibility of clot formation. The customized detachable coil,+ which consists of a very soft detachable platinum portion (0.010 in. in diameter) soldered onto a stainless steel delivery wire (0.010 in. in diameter) (Fig. 1), is intro- duced into the microcatheter with the aid of a special “Tracker 18 or 10 microcatheter and Seeker 14 or 10 micro-guidewire manufactured by Target Therapeutics, San Jose, California. t Guglielmi detachable coil manufactured by Target Ther- apeutics, San Jose, California. 10 G. Guglielmi, e7 al. BATIERY 2ACK Fic. 2. Diagram showing circuit of power supply used to produce electrothrombosis and electrolysis. LED = light-emit- ting diode; POT = potentiometer. introducer. It is then advanced through the microcath- eter into the sac of the aneurysm. Inside the microcath- eter, the platinum coil maintains a straight shape. When the coil emerges from the tip of the microcatheter, it conforms to the aneurysm lumen without causing aneu- rysmal wall distortion. The mechanical structure of the detachable coils is described in detail in Part | of this report.! Angiography is always performed before detachment in order to demonstrate the relationship of the coil to the sac of the aneurysm and parent artery. The intrinsic radiopacity of platinum delineates the position of the coil very clearly, allowing an exact evaluation of its location before electrical detachment occurs. With the platinum/stainless steel junction zone 3 mm beyond the tip of the microcatheter, a 0.5-mA, 2-V positive direct electric current (Fig. 2) is applied to the proximal end of the stainless steel delivery wire. The negative ground pole is connected to a surface or needle electrode at the groin. The positively charged intra-aneurysmal platinum coil attracts the negatively charged white blood cells, ted blood cells, platelets, and fibrinogen, thus electri- cally inducing thrombus formation. In 4 to 12 minutes, a thrombus has formed and the current has dissolved, by electrolysis, the uninsulated stainless steel junction zone so that the platinum coil is detached within the aneurysm. In order to detect the instant of detachment, the generator has a milliampere meter (Fig. 2). A sudden drop in current to 0.2 to 0.3 mA indicates that detach- ment has occurred. The stainless steel delivery wire is then withdrawn. It is possible to introduce, deliver, and detach more than one coil in the aneurysm, depending on the size of the lesion. If an undesirable placement of the plati- num coil results, it is possible to retrieve it before applying the electric current and to reposition it in a more desirable location. Currently, five types of coils are available, and are selected for use depending upon the aneurysm anatomy. They are: 1) a helix, 4 cm long and 2 mm in diameter; 2) a helix, 8 cm long and 2 mm in diameter; 3) a coil, 15 cm long with a 5-mm circular memory; 4) a coil, 20 cm long with an 8-mm circular memory; and 5) a coil, 40 cm long with an 8-mm circular memory. J. Neurosurg. / Volume 75 / July, 1991 Endovascular electrothrombosis of saccular aneurysms: Part 2 At the end of the embolization procedure, the micro- catheter is gently removed and a postembolization an- giogram is obtained in order to assess the amount of thrombosis achieved, proper placement of the detached coil(s), and patency of the parent artery and adjacent vessels. The heparinization is reversed by adminis- tration of protamine sulfate. The patients are then hospitalized for 3 to 5 days. Follow-up angiography is performed at 1 week, 3 months, and 12 months. The l-week control angiogram is obtained to assess the progression of endoaneurysmal thrombosis and the de- gree of aneurysm occlusion. Representative Cases Case 3: Acute SAH From a PICA Aneurysm This 33-year-old woman presented with SAH and a myocardial infarct. Cerebral angiography demonstrated a small saccular aneurysm arising from the left PICA (Fig. 3 /eft). The patient was not eligible for surgery due to the presence of acute myocardial infarction and pulmonary edema. Endovascular embolization and oc- clusion of the aneurysm using the detachable platinum coil technique was performed 24 hours post-hemor- rhage. Two 8-cm platinum coils with a 5-mm circular memory were delivered into the sac of the aneurysm, and electrothrombosis and electrolysis were elicited. Postembolization angiography showed almost complete obliteration of the sac of the aneurysm with a small neck remnant (Fig. 3 right). A follow-up angiogram 3 months postembolization demonstrated persistence of this small residual neck without evidence of aneurysmal growth. Surgical exploration and occlusion of the resid- ual neck with a clip was successfully performed without neurological deficits. gat wae Fic. 3. Case 3. Leff: Vertebral angiogram, lateral view, demonstrating a small aneurysm (arrow) originating from the left posterior inferior cerebellar artery. Right: Follow-up an- giogram after delivery of two detachable coils, demonstrating aneurysm obliteration. A small neck remnant (arrow) is also observed. Surgical clipping of the residual neck was performed 3 months postembolization, Case 4: Giant Basilar Bifurcation Aneurysm With Mass Effect This 60-year-old woman presented with a recent memory deficit and severe headaches. Computerized tomography (CT) demonstrated a mass in the interpe- duncular cistern, and cerebral angiography showed a giant basilar bifurcation aneurysm. Both posterior ce- rebral and superior cerebellar arteries originated from the base of the aneurysm (Fig. 4A). This aneurysm was considered inoperable due to its size and location. Via a transfemoral approach, a Tracker 10 microcatheter was positioned into the sac of the aneurysm near its dome. A nondetachable balloon was then positioned Fic. 4. Case 4. A: Vertebral angiogram, anteroposterior view, demonstrating a giant basilar bifurcation aneurysm. Both posterior cerebral arteries (straight arrows) and both superior cerebellar arteries (curved arrows) originate from the aneurysm base. B: Vertebral angiogram, lateral view, taken during the emboliza- tion procedure. A partially inflated balloon (arrowhead) was temporarily positioned in the mid-basilar artery in order to reduce blood flow. The tip of a Tracker 10 microcatheter arrow) is seen in the aneurysm dome. C: Vertebral angiogram, anteroposterior view, demonstrating seven detached coils (total length 265 cm) inside the aneurysm sac. D: Arteriogram obtained 45 days postembolization showing obliteration of the aneurysm dome. The proximal sac has been preserved in order to preserve the origin of both posterior cerebral arteries and of both superior cerebeilar arteries. J. Neurosurg. / Volume 75 / July, 1991 11 and partially inflated in the mid-basilar artery in order to decrease the possibility of coil migration due to turbulent flow (Fig. 4B). Seven platinum coils (a total of 8.5 ft) were then delivered and detached within the sac of the aneurysm by electrothrombosis and electrol- ysis. Approximately 80% of the aneurysm was filled with coils; the aneurysm neck was preserved in order to spare the origin of both posterior cerebral arteries and both superior cerebellar arteries (Fig. 4C). An angiogram performed 6 days postembolization demonstrated progressive thrombosis around the coils within the aneurysm with approximately 80% occlusion of the aneurysm volume. The neck and base of the aneurysm and the normal arteries were all preserved (Fig. 4D). A follow-up angiogram performed 40 days later showed similar results. The patient was neurolog- ically unchanged. Case 6: Acute SAH Due to Rupture of Vertebrobasilar Aneurysm This 58-year-old man presented with SAH, cardiac arrhythmia, and coronary ischemia. Cerebral angiog- raphy showed a large vertebrobasilar junction aneurysm arising from a basilar artery fenestration (Fig. SA and B). The patient was considered unsuitable for surgery due to the development of acute coronary ischemia and a background of severe generalized arteriosclerosis, A Tracker 10 microcatheter was positioned in the aneu- rysmal sac. Four platinum detachable coils (a total of 1.4 m or 4.6 ft) were then introduced into the aneurysm 12 G. Guglielmi, et al. Fic. 5. Case 6. A: Vertebral angiogram, lateral view, demonstrating a large vertebrobasilar junction aneurysm (ar- rows). B: Vertebral angiogram, anteroposterior view, show- ing this aneurysm arising from a basilar artery fenestration (arrowhead). C: Plain skull x-ray film showing the network of coils placed within the aneurysm (total coil length 1.4 m). D and E: Arteriograms obtained 6 days postembolization, lateral view (D) and anteroposterior view (E), showing 95% occlusion of the aneurysm. Residual aneurysm neck is visible (arrowhead), and the fenestrated basilar artery is now better seen (arrows). through the microcatheter (Fig. 5C). The patient toler- ated the procedure well and no neurological deficits were observed. An immediate postembolization an- giogram demonstrated that partial occlusion of the aneurysm had been obtained. A follow-up angiogram obtained 6 days postembolization demonstrated pro- gressive thrombosis of the aneurysm sac with approxi- mately 95% occlusion (Fig. 5D and E). Case 15: SAH Due to Basilar Bifurcation Aneurysm This 57-year-old woman presented with acute SAH from a ruptured small basilar bifurcation aneurysm (Fig. 6 /eft). Surgical exploration demonstrated a large posterior thalamoperforator vessel adherent to the sac of the aneurysm. It was not possible to dissect the perforator from the aneurysm sac, thus precluding sur- gical clipping. Via a transfemoral approach, a Tracker 10 microcatheter was introduced into the aneurysm sac. Complete occlusion of the aneurysm was achieved using one detachable platinum coil 40 cm long and another 15 cm long. An immediate postembolization angiogram (Fig. 6 right) and a follow-up angiogram 4 days after the procedure both demonstrated complete occlusion of the aneurysm. The patient did not develop any postembolization neurological deficits. Results Table 1 summarizes the treatment, complications, follow-up results, and outcome in this series of 15 patients. Intra-aneurysmal thrombosis ranging from 70% to 100% was achieved in all cases. Incomplete aneurysm occlusion resulted from partial coil filling of the aneurysm. The portions of the aneurysm filled with coils underwent thrombosis in 100% of cases. In this J. Neurosurg. / Volume 75 / July, 1991 Endovascular electrothrombosis of saccular aneurysms: Part 2 if a, Fic. 6. Case 15. Left: Vertebral angiogram, anteropos- terior view, demonstrating a small basilar bifurcation aneu- rysm, Right: Vertebral angiogram obtained 4 days postem- bolization showing complete aneurysm obliteration with two detachable platinum coils. Note that these coils assume the original shape and size of the aneurysm without deforming it. series there was one transient neurological deficit (apha- sia in Case 5); no permanent deficits or deaths occurred. Discussion Two percent of the entire population of the United States will have an intracranial aneurysm; such an intracranial aneurysm will rupture in less than 1% of the population and will be the cause of death in 0.5%. In North America, 25,000 intracranial aneurysms rup- ture every year followed by bleeding into the subarach- noid space or cerebral tissue.” The primary purpose of treatment for ruptured intracranial aneurysms is to pre- vent rebleeding, which in most cases would be catas- trophic. Electrothrombosis of aneurysms has previously been reported by Mullan’ in 1974, With a stereotactic probe, he was able to introduce very fine copper-plated steel needles across the neck of the aneurysms; thrombosis was initiated by passing a direct electric current through each needle for 5 minutes. He concluded from the results that the technique in selected cases was compa- rable but not necessarily superior to standard surgical methods. This technique has not become very popular because the aneurysm has to be punctured, extensive equipment is required, and it is necessary to penetrate cerebral tissue in order to reach the aneurysm with the probe. The endovascular approach to aneurysm occlusion has previously been limited to balloon embolization.?* This method of embolization has the special advantage of avoiding general anesthesia, craniotomy, and brain manipulation. However, the main disadvantage is that the fragile wall of the aneurysm undergoes stress while adapting to the shape of the balloon, thus carrying the risk of aneurysm rupture. This risk may be higher in J. Neurosurg. / Volume 75 / July, 1991 the acute post-hemorrhagic phase. In a series of 84 inoperable patients treated by balloon embolization with preservation of the parent artery, Higashida, et al. reported a 17.9% mortality rate and a 10.7% morbidity rate directly related to the embolization pro- cedure. A less traumatic approach has been developed, which consists of a very soft detachable platinum coil soldered to a stainless steel delivery wire. It has the advantages of the endovascular approach and it is also usable in the acute post-hemorrhagic phase. This device and the electrochemical basis on which its function is based are described in Part 1 of this report.' In our series of 15 patients treated with endovascular electrothrombosis by means of detachable coils, all aneurysms were consid- ered to be difficult and at high risk for surgery (Table 1). Balloon embolization was not used because it is believed that detachable coils are less traumatic than balloons and that endovascular electrothrombosis car- ries less risk of rupturing an aneurysm, especially in the acute phase after SAH. Furthermore, in three instances (Cases 4, 5, and 13) balloon embolization would have led to occlusion of normal vessels arising from the aneurysm base. In this preliminary clinical experience, no permanent neurological deficits and only one occurrence of tran- sient aphasia (Case 5) have been observed after embol- ization. It has been possible to achieve complete aneu- rysm occlusion in two patients (Cases 14 and 15) and satisfactory aneurysm occlusion in four (Cases 3, 6, 11, and 13). In the remaining cases the aneurysm neck was too wide (and/or normal arteries were arising from the aneurysmal sac) to achieve complete aneurysm oc- clusion. Intra-aneurysmal thrombosis progresses with time. It is believed that this is due to two factors: 1) in the hours that follow embolization more blood components are trapped within the network of coils; and 2) during the procedure systemic heparinization impedes intra-aneu- rysmal clot formation and, as soon as heparin is re- versed, clot formation within the coils is enhanced. It is believed that, aside from producing electrothrom- bosis, the coils represent a packing material that holds the intra-aneurysmal thrombus and prevents both its displacement into the parent artery and its fragmenta- tion. This inhibits distal embolization. In all but one case, the parent vessel was preserved. This result was achieved mainly because it is possible to withdraw the coil back into the microcatheter if an unsatisfactory position in the aneurysm has been achieved. It is then possible to try again with the same coil or with a different-sized one to achieve better intra-aneurysmal coil placement. A major goal in the management of ruptured intra- cranial aneurysms is to treat the patient as soon as possible after admission to the hospital, possibly within 2 days after SAH. The recently published results of the International Cooperative Study on the Timing of An- eurysm Surgery’ confirm that early surgery (1 to 3 days 13 after SAH) carries more operative risks than delayed intervention. On the other hand, delayed intervention is associated with lower morbidity and mortality rates, but many patients die while waiting for the optimum time for surgery (subsequent to Day 10 post-SAH) because of rebleeding. With the device described here, implantable at the time of the diagnostic angiogram, it may be possible to avoid early rebleeding. In this preliminary experience with 15 patients, the follow-up period is short (Table 1). This is because the technique has only recently been applied in the clinical setting: the first procedure was performed clinically on March 6, 1990. Long-term angiographic and clinical follow-up monitoring is necessary to achieve an accu- rate idea about the advantages and limitations of this newly developed aneurysm occlusion device. Acknowledgments The authors thank Drs. Neil Martin, Robert Rand, Steven Giannotta, Pedro Lylyk, Marco Zenteno, Imre Weitzner, Charles Strother, and Linda Chi for their support. They are also grateful to Ms. Mari Triana who assisted in the prepara- tion of the manuscript. References 1. Guglielmi G, Vifiuela F, Sepetka I, et al: Electrothrom- bosis of saccular aneurysms via endovascular approach. Part 1: Electrochemical basis, technique, and experimen- tal results. J Neurosurg 75:1-7, 1991 2. Hieshima GB, Higashida RT, Wapenski J, et al: Balloon 14 G. Guglielmi, et al. embolization of a large distal basilar artery aneurysm. Case report. J Neurosurg 65:4 13-416, 1986 3. Higashida RT, Halbach VV, Barnwell SL, et al: Treat- ment of intracranial aneurysms with preservation of the parent vessel: results of percutaneous balfoon emboliza- tion in 84 patients, AJNR 11:633-640, 1990 4. Hunt WE, Hess RM: Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 28:14-20, 1968 5. Kassell NF, Torner JC, Haley EC Jr, et al: The Interna- tional Cooperative Study on the Timing of Aneurysm Surgery. Part 1: Overall management results. J Neurosurg 73:18-36, 1990 6. Kassell NF, Torner JC, Jane JA, et al: The International Cooperative Study on the Timing of Aneurysm Surgery. Part 2: Surgical results. J Neurosurg 73:37-47, 1990 7. Mullan S: Experiences with surgical thrombosis of intra- cranial berry aneurysms and carotid cavernous fistulas. J Neurosurg 41:657-670, 1974 8. Romodanov AP, Shcheglov VI: Intravascular occlusion of saccular aneurysms of the cerebral arteries by means of a detachable balloon catheter. Adv Tech Stand Neu- rosurg 9:25-48, 1982 9. Weir B: Intracranial aneurysms and subarachnoid hem- orrhage: an overview, in Wilkins RH, Rengachary SS (eds): Neurosurgery. New York: McGraw-Hill, 1985, Vol 2, pp 1308-1329 Manuscript received December 1, 1990. Accepted in final form February 18, 1991. Address reprint requests to: Guido Guglielmi, M.D., Univ- ersita’ di Roma, Dipartimento di Scienze Neurologiche, Neu- roangiografia Terapeutica, Viale dell'Universita’ 30/a, 00185 Roma, Italy. J. Neurosurg. / Volume 75 / July, 1991