Electrically Induced Thrombosis in Intracranial Aneurysms* S. ]~r M.D., A. J. RAIMONDI,M.D., G. DOBBEN, M.D., G. VAILATI, M.D., AND J. HEKMATPANAH,M.D. Division of Neurological Surgery and Department of Radiology, University of Chicago Clinics and Hospitals, Chicago, IUinois hE occasional observation of spontaneous occlusion of an intracranial aneurysm has suggested the possibility of a surgically induced thrombosis (Fig. 1). Labor a t o r y studies have shown t h a t thrombosis could be produced very easily in arLificial aneurysms of the femoral artery of the dog b y passage of a small direct electrical current across the sac. Thrombosis in an intact femoral artery required the insertion of an intra-al~terial anode and a current of 50 to ~,000 gA. for a period of a b o u t 1 to ~ hrs. This clot lasted only a few days and in the course of its development it was subject to embolization if the current was too strong, if the negative electrode was too close, or if the animal m o v e d its leg while the needle was in place. Epsilon-aminocaproic acid prolonged the duration of the clot. 1,2 As one of us had punctured, w i t h o u t hemorrhage, two aneurysms exposed at open operation b y insel~ing into t h e m a needle ~0 mils in diameter (s gauge), it seemed t h a t p u n c t u r e b y an extremely fine electrode 4 mils in diameter would be safe. W i t h d r a w a l offered no problem since it was k n o w n t h a t the steel tip would erode during passage of a current of sufficient strength and duration to produce thrombosis. I t was believed t h a t the electrode could be inserted through a burr hole and guided to the aneurysm b y biplane r a d i o g r a p h y and thus a major craniotomy in the early period following hemorrhage could be avoided. Because of the dangers of embolism and of thrombosis of the parent vessel, serial angio g r a p h y during the procedure seemed indicated. I t was felt also t h a t the operation T Received for publication May 21, 1964. * Aided by the United States Public Health Service General Research Support Grant 1-S01-FR-50367-01, and MO 1-F.R.-55. should be done under local anesthesia so t h a t any clinical deterioration as the result of excessive contrast material or excessive thrombosis or embolization could be determined at the earliest possible m o m e n t . Successful thrombosis b y this relatively simple technic m i g h t be expected to carry the patient safely t h r o u g h the critical early weeks without fear of recurrent hemorrhage and enable definitive surgery to be undertaken at the time of election. T h e possibility that permanent thrombosis m i g h t occur in some instances was entertained. Technic The special steel electrodes* had an insulated shaft 10 mils in diameter and an uninsulated end 4 mils in diameter. The length of the uninsulated end was determined by pre-operative study of the aneurysm. It was usually 4 to 7 mm. in length and was made exquisitely sharp. After shaving the patient's head, a burr hole was made (under local anesthesia) at a site convenient to the aneurysm. The skin and muscle were closed. Next the head was fixed by a threepronged head-holder which gripped the bone. This holder was fairly firm but not so firm as desirable. One copper grid was fastened on the skin of the lateral surface of the skull remote from the aneurysm, and a second was attached to the occiput. The common carotid artery was punctured and a catheter was threaded up to the bifurcation. Occasionally a simple needle puncture was used and on two occasions the carotid artery was catheterized through the femoral artery. Biplane arteriography outlined the aneurysm on the two surface grids. The introducing needle (usually gauge s was inserted manually through the skin overlying the burr hole and was advanced and repositioned until its image fell upon the exact point of the grids occupied by the aneurysm. Each movement was checked by biplane radiography (without contrast).~ Finally biplane angiog* Supplied through the courtesy of Ethicon, Inc. t Supplied by courtesy of Polaroid Corporation Xray Technical Service Department. 539 540 Mullan, Raimondi, Dobben, Vailati and Hekmatpanah FIG. 1. Twenty-three years previously patient had headache and palsy of the 3rd nerve from which he made a subtotal recovery. Left shows calcification adjacent to posterior clinoid. Right shows that this area does not fill with contrast material. raphy was taken to make sure the grids or headholder had not moved (and sometimes they had). If necessary, further adjustments and further angiography were undertaken. Usually it took 5 or 6 movements of the needle, but sometimes it took 10 or le, and once only ~ movements were necessary. I t was not difficult to get the needle to within ~-8 ram. of the target, but it took time to get it to the exact fraction of an ram. t h a t was necessary. As the lengths of the introducing needle and of the electrode were known, the position of the point of the electrode relative to the aneurysm could be determined by measuring the amount t h a t protruded beyond the introducing needle. W h e n the sharp electrode touched the aneurysm, a sensation of resistance was encountered. Sometimes a slight flick of pain was experienced. The position was checked again b y measurement and the needle was then inserted to the desired depth. I n most instances this produced a slight pain, but as the patients were warned of this and as it was only slight, there were no problems. The current was turned on and serial angiograms were taken every 80 rain. until satisfactory thrombosis was achieved (Fig. ~). As the point of the needle wears away within 15 rain. or so, the thrombotic process m a y be accelerated b y replacing needles, but this was done no oftener t h a n every 30 min. to make sure t h a t an intact needle was not being pulled out. The tips of the needle are too fine to be seen radiographically. Angiography was sometimes performed at increasingly frequent intervals towards the end of thrombosis. Results T h e c a s e h i s t o r i e s of 1~ p a t i e n t s w h o h a v e b e e n t r e a t e d b y t h i s m e t h o d are p a r t l y s u m m a r i z e d in T a b l e 1. T h e y were u n s e l e c t e d , since n o o t h e r m e t h o d w a s u s e d t o t r e a t a n e u r y s m s in p a t i e n t s w h o were a d m i t t e d t o o u r s e r v i c e d u r i n g t h i s p e r i o d of t i m e . T h e l a s t 3 p a t i e n t s w e r e t o o ill t o t r e a t b y c o n v e n tional surgical methods. There were 7 aneur y s m s of t h e i n t e r n a l c a r o t i d a r t e r y a t t h e posterior communicating junction, ~ on the anterior communicating artery, e on the a n t e r i o r c e r e b r a l a r t e r y a t t h e g e n u , a n d I on the middle cerebral artery. Ten patients had s u f f e r e d one or m o r e s u b a r a c h n o i d h e m o r r h a g e s a n d 8 of t h e s e h a d b e e n in c o m a . I n 1 ( C a s e 9) p a l s y of t h e 3 r d n e r v e d e v e l o p e d a n d 1 ( C a s e 4) h a d s u d d e n loss of consciousness. T h e f o l l o w - u p i n t e r v a l r a n g e s b e t w e e n 6 a n d 14 m o n t h s . N o n e h a s b l e d in t h e i n t e r val. Follow-up angiography has been prov i d e d for C a s e s 2, 3, 4, 5, 6 a n d 8. T h i s shows t h a t in t h o s e in w h o m t h r o m b o s i s w a s c o m p l e t e (Cases ~ a n d 3) s u b t o t a l t h r o m b o s i s p e r s i s t e d o v e r t h e d u r a t i o n of t h e f o l l o w - u p , b u t t h a t in t h o s e in w h o m i t w a s s u b t o t a l , it disappeared quite early. Three patients ( C a s e s 1, 3 a n d 4) h a d s u b s e q u e n t c l i p p i n g of their aneurysms. B r i e f case h i s t o r i e s of 6 p a t i e n t s will s e r v e t o i l l u s t r a t e t h e m e t h o d a n d s o m e of its problems. Case Reports Case 1. S.J., a 4e-year-old woman, had a sub- arachnoid hemorrhage 10 days before admission. There was a large aneurysm on the right internal carotid artery at the posterior communicating Electrically Induced Thrombosis in Aneurysms 541 FIG. 2. Case 10. Progressive thrombosis of aneurysm of genu of anterior cerebral artery over a period of 135 rain. Current starting at 200 was gradually increased to 2,000 ~A. junction. Two p l a t i n u m electrodes, insulated except at their tips, were passed through 2 burr holes so as to touch the external surface of the aneurysm. Epsilon-aminocaproic acid was given intravenously at the rate of 500 mg. per hr. A current of 200 #A. was used first and then increased by steps over ~ hrs. to ~,000 #A. I t was maintained for a total of 689 hrs. Final angiography showed subtotal thrombosis of the aneurysm (Fig. 3). The procedure was discontinued at this point and it should be noted that the patient received a total of 200 cc. of contrast material.* Eleven days later the aneurysm was clipped surgically. I t bled during clipping. I t could not be certain whether any clot was still present. The wall was not thickened. limits, a n d t h a t s u c h e x t e n s i v e a n g i o g r a p h y m i g h t , in t i m e , p r o d u c e its o w n h a z a r d s . C o m m e n t . I t was c o n c l u d e d f r o m Case 1 t h a t electrodes a p p l i e d e x t e r n a l l y l e n g t h e n e d the operative procedure beyond reasonable Case 2. M.T., a 80-year-old housewife, complained of sudden severe headache and stiffness of her neck 9 days before the birth of her child. She had another hemorrhage during labor. Angiography showed a bilobed aneurysm on the internal carotid artery at the posterior communicating junction on the left. Seventeen days after delivery the aneurysm was thrombosed (after 62 min.), using an intra-arterial steel electrode and ~,000 #A. current. She was given 24 gm. of epsilonaminocaproic acid daily for 6 weeks. Two weeks, 6 weeks, and 7 months later angiography showed that the proximal lobe of the aneurysm had refilled, b u t that the distal lobe remained obliterated (Fig. 4). She is very well 9 months later. * Hypaque supplied through the courtesy of Winthrop Laboratories. Case 3. A.P., a 14-year-old boy, had a hemorrhage from an aneurysm of the left internal earot- Mullah, Raimondi, Dobben, Vailati and Hekmatpanah 54~ TABLE 1 Histories of 12 patients treated by electrically induced thrombosis in intracranial aneurysms I Name Age (Yrs.) Site Current ] Days Since l,ast [Hemorrhage Pre-operative Deficit pA. I Final Neurological Deficit Postoperative Deficit Time (Mins.) 1. S.J.* 4~ ICPC l0 Nil ~00-~000 390 Nil Nil ~. M.T. 30 ICPC 17 Transient semicoma ~000 6~ Nil Nil 3. A.P. ICPC Paralysis 3rd nerve ~000 ~50 Paralysis Srd nerve Nil 4. H.W. 53 MC 13 Transient hemiplegia after angiography ~00-~000 105 Transient hemiplegia Nil 5. L.A. 37 A con 19 Coma. Confusion ~000 110 Transient hemiplegia Nil 6. L.C. 38 ICPC 1 Coma. Confusion. Hemiparesis ~000 80 Deepened hemiparesls. Aphasia Minimal hemipares!s. Some dysphasia 7. O.J. 44 ICPC 18 Coma twice. Severe confusion. Dysphasia ~000 90 Hemiparesls. Severe dysphasia Minimal dysphasia 8. R.C. 33 A eon~ 3 Coma, transient ~000 1~0 Transient "akinetie mutism" Nil 9. M . J . ICPC ~:3 3rd nerve ~00 ~000 135 Hemiplegia. Aphasia tiemlparesls. Dysphasia 10. P.S. 4O AC ge 5 Akinetle mute ~000 1S5 Akinetie mute Nil 11. II.S. 45 AC ge ~0 Coma. Total confusion ~000 90 Severe mental impairment Severe mental impairment 1~. D.R. [C 13 Coma. Severe confusion ~000 90 Hemiparesis Death 33 4'2 * Electrodes extend to aneurysm. In all other instances the anode pierces the sac. AC =Anterior cerebral ICPC =Internal carotid, posterior communicating junction A com. =Anterior communicating MC =Middle cerebral IC =Internal carotid X = N o definite pre-operative hemorr]mge. Time indicates duration of symptoms F I G . 3. Case 1. T o p r i g h t : l a t e r a l v i e w . All o t h e r s a r e a n t e r o p o s t e r i o r v i e w s of a n e u r y s m of i n t e r n a l c a r o t i d a r t e r y . B o t t o m r i g h t s h o w s s u b t o t a l t h r o m b o s i s a f t e r 689 h r s . , ~ 0 0 - 2 , 0 0 0 ~ A . Electrically Induced Thrombosis in Aneurysms 543 FIG. 4. Case 2. Top, anteroposterior and lateral views of aneurysm before thrombosis. Note bilobed appearance on anteroposterior view. Middle, reappearance of aneurysm ~, weeks after complete obliteration. Note persistence of neck only. Bottom, appearance after 7 months. Fro. 5. Case 3. Lateral view of aneurysm of internal carotid artery showing progressive thrombosis. 544 Mullan, Raimondi, Dobben, Vailati and Hekmatpanah FIo. 6. Case 3. Top left, anteroposterior view; top right, lateral view pre-operatively. Bottom left, anteroposterior view, Bottom right, lateral view 8 wks. after thrombosis. id artery. There was slight hemiparesis. His aneurysm was thrombosed by 2,000 ~tA. over a period of 370 miu. (Fig. 5). The palsy of the 3rd nerve disappeared b u t returned 55 days later. Arteriography showed recurrence of a smaller aueurysm (Fig. 6). I t was clipped, and he remains very well. Case 5. L.A., a 37-year-old woman, lost consciousness on the day of admission. Seven days later she was thought to be well enough for angiography, and 19 days later the aneurysm of the anterior communicating artery was thrombosed. A sudden left hemiplegia developed 110 rain. after turning on a 2,000/~A. current. Angiography at that moment showed obliteration of the aneurysm and failure of filling of the anterior cerebral artery on the right side. Within 15 rain. her left hand was moving well and 7 days later the leg had regained full strength. Two weeks after the operation angiography showed good filling of the right anterior cerebral artery, and subtotal occlusion of the aneurysm. She remains well 8 months afterwards (Fig. 7). Case 8. R.C., a 33-year-old man, was found in an unconscious state. There was no movement of the left side of his body. Two days later his strength had returned and he was able to converse. Following angiography there was a return of hemlparesis to the left side. Next day this had disappeared again and the aneurysm of the an- terior communicating artery, which filled from the right, was ~ thrombosed when he became too uncooperative to proceed further. For the next 14 days he was quite lethargic and at times akinetic and mute. Angiography at this period showed partial refilling of the aneurysm (Fig. 8). About 1 month after the procedure he was fairly well b u t still not so alert as normally. The aneurysm was then clipped. He has made a complete recovery and has returned to work driving a heavy truck. Case 9. ~r a 33-year-old woman, had severe headaches and palsy of the 3rd nerve. She was given epsilon-aminocaproic acid, 1~ gm. daily, for 5 days. Her aueurysm was thrombosed b y a gradually increasing current (up to 2,000/zA.) over a period of 135 min. At the end of the procedure she had a right hemiparesis and dysphasia without obvious cause. Epsilon-aminocaproic acid was continued. Five days later these signs increased and the epsilon-aminocaproic acid was stopped. During the next 5 days she improved and epsilon-aminocaproic acid was recommenced. A few days later hemiparesis suddenly became complete and she was aphasic. Epsilon-aminocaproic acid was stopped again. She has made a moderate recovery over a period of 9 months. Discussion T h e r e were 19 needle p u n c t u r e s i n this series, s o m e a n e u r y s m s h a v i n g t h e electrode Electrically Induced Thrombosis replaced as it wore away. N o n e bled during the procedure and none bled during the period of follow-up. Thus it would appear t h a t the m e t h o d achieves its p r i m a r y objective which is prevention of early recurrent hemorrhage. In 4 of the 11 survivors it must be noted t h a t the procedure was performed on the 17th, 18th, 19th and ~0th day after the last hemorrhage and only minimal success can be claimed for these. T h e next question is how long does this apparent " p r o t e c t i o n " last? I n those 6 patients in whom neurological deficit was absent or absolutely minimal, and in whom it was felt t h a t follow-up angiography offered no hazard to recovery, it was found t h a t the thrombi were in all instances temporary, though in Cases ~ and 3 (Figs. 4 and 6) some filling defect remained. I t was t h o u g h t t h a t there was microscopic evidence of thickening of the wall in Case 3 when the a n e u r y s m was subsequently clipped b y open craniotomy, and t h a t there was histological evidence of thickening in Case 7 (who died later of a unrelated cause without evidence of recent intracranial hemorrhage). T h e evidence for late protection is, however, meager and in the absence of more positive assurance must not be assumed. T h e next question is the price of this " t e m p o r a r y " freedom from recurrent hemorrhage in terms of m o r t a l i t y and morbidity. Three patients (Cases 10, 11 and 1~) were too ill for surgery b y conventional technics. T h e patient who died (Case 1~) was v e r y obese and hypertensive (~50/110). After 13 days in varying stages of coma he was just beginning to respond at the time of operation. Following the procedure he had some left-sided weakness. N e x t day he remained drowsy, but responded and used his left limbs. T h a t evening he died. Autopsy was refused, and we can only speculate t h a t swelling of the brain developed as a result of the contrast material (48 cc. in 6 cc. doses), t h a t the electrical current t h r o m b o s e d some of the perforating vessels close to the aneurysm, t h a t microembolism occurred or t h a t the thrombus spread into the main artery. B o t h of the other severely ill patients in Aneurysms 545 FIG. 7. Case 5. Top, before thrombosis. Middle, immediate]y after. Bottom, ~ wks. after. (Cases 10 and 11) had aneurysms on the anterior cerebral a r t e r y at the genu. One was akinetie and m u t e and the other was almost in this state. T h e i r condition remained unchanged postoperatively and their defects cannot be a t t r i b u t e d to the procedure. One has since (9 months) made an excellent mental recovery. In 1 patient (Case 9) who received epsilonaminocaproic acid before, during, and after thrombosis severe hemiplegia and aphasia developed, and it m a y be t h a t excessive thrombosis was related to this drug. This is 546 Mullan, Raimondi, Dobben, Vailati and Hekmatpanah FIG. 8. Case 8. Anteroposterior views. Left, before; middle, after; right, 4 wks. after thrombosis. only speculation, since the patient (Case ~) who also received the drug had no complications. I t might be held that epsilon-aminocaproic acid was instrumental in securing the partial p e r m a n e n c y of the thrombus in Case (9-months obliteration of the distal lobe of a bilobed aneurysm), but our other patient (Case 3), who showed prolonged diminution in the size of the aneurysm, did not have any. The role, therefore, of epsilon-aminocaproic acid in the t r e a t m e n t of these patients is not yet clear. In 4 other patients hemiplegia or hemiparesis developed during the procedure. In 1 (Case 4) it m a y have been caused by an embolus liberated from the site of puncture of the carotid a r t e r y in the neck, or from the aneurysm and it cleared within a minute. I n another (Case 5) it was clearly related to thrombosis of the adjoining anterior cerebral artery. Weakness disappeared within 7 days and the anterior cerebral artery was shown to be patent when arteriography was performed at the end of 14 days. In e others (Cases 6 and 7) a slight neurological deficit t h a t existed before the procedure deepened during thrombosis and t h e n almost cleared after a period of 3 months. T h e cause of these complications remains obscure and, as in the case of fatal issue, we must suspect contrast material in a patient who had previous neurological weakness, thrombosis of adjoining small perforating vessels, microembolism and excessive spread of thrombosis. We have given s cc. of H y p a q u e in 6 cc. doses over a period of 6 hrs. to a patient (Case 1) who had no neurological deficit, but we do not know the safe level in the presence of a deficit. In general, the more severe complications develop in those who had the most severe preoperative defects (except in Case 9). Spread of thrombus into the main stream is not the most likely explanation because some weakness was detected at a late stage of thrombosis when arteriography showed t h a t the main vessels were patent (except in Case 5). T h e ease with which very small vessels could be thrombosed was observed frequently in our expe~'iments with animals and points to the possibility of thrombosis of small perforating arteries. This might very well be the explanation of the severe postoperative mental changes in the patient in Case 8, who was mentally clear before t h r o m bosis of his anterior communicating aneurysm. F o r ~ weeks afterwards he spoke rarely, though he could speak, and he was a p p a r e n t l y unconcerned about his illness. H e seemed to have a minor degree of the syndrome of akinetic tourism b u t fortunately made a full recovery. I n j u r y b y contrast material or b y microembolization shouhl have produced evidence of unilateral impairmerit in his case. Angiography during the procedure showed subtotal occlusion of the a n e u r y s m only and no obstruction to major arteries a t the end of the procedure when confusion was already evident. We, there- E l e c t r i c a l l y I n d u c e d T h r o m b o s i s in A n e u r y s m s fore, suspect that thrombosis of these small, perforating vessels may have been a significant factor in this and in some Of our other complications. Though the observation may not be of great importance, it may be noted that, of those patients who had aneurysms of the internal carotid artery at the posterior communicating junction, those with large sacs which extended laterally (Cases 1, 2 and 3) had less complications than those with short, small sacs more directly behind the internal carotid artery (Cases 6, 7, 9 and 12). Summary 1. Twelve patients had electrically induced thrombosis of their intracranial aneurysm utilizing slender, sharp electrodes introduced manually through a burr hole under biplane radiographic control. 2. One died. 3. None has rebled during the follow-up 547 interval, which ranges from 6 to 14 months. 4. In 5 patients hemiparesis or hemiplegia developed during the procedure. Two have made a complete recovery; 2 made a virtually complete recovery; and 1 remains hemiparetic. Mental slowing developed in 1 patient, but a complete recovery was made. 5. Follow-up angiography has been performed in 6 patients: 2 showed complete refilling of the aneurysm at 3 and 4 weeks; 1, 50 per cent filling at 289 weeks; 1, 10 per cent filling at 2 weeks; and 2, 40 per cent refilling, 1 at 8 weeks and 1 at 2, 6 and 28 weeks. References 1. MUI_I.AN, S., BECKMAN, F., and VAILATI, G. Simplified thrombosis of a large hypertrophic hemangioma of the scalp. J. Neurosurg., 1964, 21: 68-7!~. ~. MULLAN, S., BECKMAN, •., VAILATI, G., KARA~ SICK, G., and DOBBEN, G. An experimental approach to the problem of cerebral aneurysm. J. Neurosurg., 1964, 21 : 838-845.