J Neurosurg 74:205-211, 1991

Management of hemorrhagic complications from preoperative embolization of arteriovenous malformations PHILLIP D. PURDY, M.D., H. HUNT BATJER, M.D., AND DUKE SAMSON, M.D. Division of Neuroradiology, Department of Radiology, and Departments of Neurosurgery and Neurology, University of Texas Southwestern Medical Center, Dallas, Texas I Endovascular embolization procedures have undergone dramatic evolution and improvement in recent years. Despite these advances, controversy remains regarding the optimal role of these procedures in treating cerebral arteriovenous malformations (AVM's) and whether their purpose should be as a presurgical adjunct or as primary therapy. This controversy risks fragmentation between disciplines in the broader efforts to improve management of cerebrovascular disorders. The authors report seven cases of life-threatening hemorrhages that occurred during staged invasive therapy for AVM's which illustrate the value of a unified team approach to optimize patient care. Each patient underwent at least one embolization procedure using polyvinyl alcohol particles, followed in two cases by the occlusion of proximal feeding vessels by platinum microcoils and in one case by the attempted detachment of an endovascular balloon. In three patients, catheter penetration into the subarachnoid space resulted in subarachnoid hemorrhage. One patient suffered rupture of a large feeding vessel during balloon inflation. The final three patients sustained intracranial hemorrhage 2 hours, 8 hours, and 5 days, respectively, following embolization. All but two patients underwent emergency craniotomy at the time of the complication. These cases underscore the advantages of interdisciplinary management optimizing decision-making and providing expeditious care when life-threatening complications develop. KEY WORDS •

arteriovenous malformation • embolization • endovascular therapy •

hemorrhage

of arteriovenous malformations (AVM's), both primarily and for preoperative devascularization, has been discussed extensively during recent years. 1.5.6.11,1214-16 The initial development of catheter intracerebral embolization utilized calibrated-leak balloons, 1° necessitating the use of liquid embolic materials. Hence, isobuty1-2-cyanoacrylate (IBCA) has dominated as an embolic material.' With the introduction of polyvinyl alcohol (PVA), 17 a new embolic material became available. The recent availability of n-butyl-cyanoacrylate,' ethanol with microfibrillar collagen material,' surgical silk,' and platinum microcoils7 has led to the introduction of a wide array of chemicals and devices for embolization. Although embolization is often used in conjunction with surgery, little specific attention has been given to the interaction between neurosurgeons and neuroradiologists in the diagnostic, planning, embolization, and operative phases of management of AVM's. In fact, increasing fragmentation is occurring in these closely

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parallel disciplines. Little discussion can be found regarding the role of the neurosurgeon in the management of complications of embolization, when they occur. We report our experience with seven cases of potentially catastrophic hemorrhage that occurred during or within a few days after embolization and discuss the role of immediate surgical extirpation of the AVM when hemorrhage is encountered. Clinical Material and Methods

Seven patients treated for intracranial AVM's at the University of Texas Southwestern Medical Center at Dallas since 1985 have developed intracranial hemorrhagic complications during planned staged embolization and resection of their malformations. This group represents 11% of the 63 patients with cerebral AVM's treated by embolization during that interval. Of these seven patients, two died as a consequence of the hemorrhage, one has significant residual neurological im205

P. D. Purdy, H. H. Batjer, and D. Samson pairment, and the other four developed no significant residual impairment as a consequence of their hemorrhagic complication. Particulate Embolization After systemic administration of heparin (5000 U), anticoagulation was maintained throughout the embolization procedures with additional boluses of 1000 U/ hr. Embolization was performed via selective catheterization of intracerebral feeding branches. Initially, the vertebral or internal carotid arteries were catheterized in standard fashion. Utilizing a coaxial system, Tracker18 catheters* were then advanced to the appropriate branches of the middle, anterior, or posterior cerebral feeding arteries adjacent to the malformation. After angiographic verification of placement, embolization was performed using PVA foam particles varying in size, usually between 300 to 500 A and 1 to 1.5 mm. Since the introduction of platinum microcoil devices, we have utilized them routinely in addition to the PVA foam and, once stasis was observed within the malformation, the feeding vessel was occluded with microcoils. Our techniques have been described in more detail elsewhere.' 3 In one case, following embolization with small PVA particles, a flow-directed detachable silicone balloon was used to occlude the embolized feeding vessel. In routine cases, after satisfactory angiographic stasis was noted, the entire coaxial system was removed. The catheter was then flushed and the carotid or vertebral artery was again catheterized for postembolization angiographic study. Anticoagulation was reversed with protamine (50 mg) at the termination of the embolization procedure, before removal of the arterial sheath. Several patients have required multiple procedures, with as many as four in one patient. Illustrative case reports and a summary of the overall results are presented below. Case Reports Case 1 This 30-year-old right-handed man developed an adult-onset seizure disorder. Computerized tomography (CT) scanning and cerebral angiography showed a moderate-sized medial right frontal AVM fed by the anterior cerebral and middle cerebral arteries (Fig. I left). On August 25, 1987, the patient was taken to the angiography suite where a Tracker-18 catheter was placed into the right pericallosal feeding artery to the malformation for planned embolization. Following angiographic verification, embolization with PVA particles was begun. During that procedure the catheter was noted by fluoroscopy to withdraw slightly out of the feeding branch into the pericallosal trunk. Subse-

* Tracker-18 catheter manufactured by Target Therapeutics, San Jose, California.

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quently, the catheter was repositioned but, on test injection, contrast medium was seen to extravasate into the callosal cistern (Fig. 1 center and right). The patient complained of immediate headache but did not lose consciousness or develop a focal neurological deficit. Due to the apparently extravascular tip, the catheter was left in place and protamine (50 mg) was administered to reverse the heparinization. The patient was taken immediately to the operating room with the catheter still in place. After general endotracheal anesthesia was induced, a bicoronal scalp flap was performed followed by a large right parasagittal frontal craniotomy. Following dural opening, the brain was found to be tense with obvious evidence of subarachnoid hemorrhage (SAM. An interhemispheric microsurgical approach was performed exposing the corpus callosum and identifying the pericallosal artery. This vessel was followed and the point of catheter penetration was seen in the subarachnoid space, with the catheter tip having exited the pericallosal artery on the distal aspect of the origin of the perpendicular feeding artery. A curved aneurysm clip was positioned across the origin of that feeding artery and, as the catheter was withdrawn transfemorally, the clip was closed. There was no resultant hemorrhage and the distal pericallosal artery was inspected carefully and found to be patent. A cortical incision was then made on the medial aspect of the frontal lobe at the anterior margin of the malformation and extended laterally into the periventricular region. Dissection was extended circumferentially around the interhemispheric representation of the malformation into the lateral ventricle. This dissection eliminated all anterior cerebral and middle cerebral feeding arteries and the AVM was extirpated medially, hinged on its venous drainage. After routine closure, blood loss was estimated at 400 cc and there was no intraoperative transfusion. The patient underwent a definitive postoperative arteriogram disclosing that the malformation was completely resected. He was discharged from the hospital on the 5th postoperative day neurologically intact. Case 5 This 20-year-old right-handed man was initially evaluated due to episodes of bizarre behavior and a generalized seizure disorder. Magnetic resonance (MR) imaging and CT showed a large left frontal AVM (Fig. 2A). Angiography demonstrated a very high-flow lesion irrigated by an enlarged ascending frontal branch of the middle cerebral artery as well as numerous other branches arising from the middle cerebral bifurcation region (Fig. 2B). Substantial anterior cerebral artery contribution was also present. The family was adamant that the lesion be treated and, on July 27, 1989, the patient was taken to the angiography suite where the major left middle cerebral artery branch was embolized with PVA particles and microcoils until stasis was achieved. An anterolateral segment of the AVM clearly developed a filling defect. J. Neurosurg. Volume 74 / February, 1991

Hemorrhage from interventional embolization

FIG. I. Case I. Left: Right internal carotid angiogram, lateral view, demonstrating a 4-cm medial frontal arteriovenous malformation irrigated by the anterior and middle cerebra] arteries. During embolization, the patient complained of increased headache following catheter repositioning. Center and Right: Test injection (lateral (center) and anteroposterior (right) views) revealing subarachnoid extravasation of contrast medium.

FIG. 2. Case 5. A: Pretreatment magnetic resonance image revealing left frontal arteriovenous malformation (AVM) involving the lateral ventricle. B: Left internal carotid angiogram showing major irrigation by left middle cerebral artery branches. C: Angiogram after the second embolization procedure confirming reduction in filling of the AVM. D: Emergency computerized tomography (CT) following sudden headache and obtundation revealing a large frontal hematoma. E: Left carotid angiogram obtained postoperatively confirming complete AVM excision. F: Postoperative CT scan illustrating the extent of frontal resection.

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P. D. Purdy, H. H. Batjer, and D. Samson The patient remained neurologically well and, on August 3, underwent further embolization. At that time, additional left middle cerebral artery branches were embolized successfully (Fig. 2C). Two hours following the embolization procedure he developed the sudden onset of severe headache and became obtunded. A CT scan demonstrated a large left frontal hematoma with intraventricular extension (Fig. 2D). He was taken immediately to the operating room after urgent intubation, hyperventilation, and the induction of etomidate coma. A large left frontal craniotomy was urgently performed disclosing a swollen and tense frontal lobe. As the venous drainage projected posteriorly just superior to the sylvian fissure, the posterior cortical incision for a planned frontal lobectomy was begun immediately adjacent to the vein at the posterior cortical representation of the malformation. As the cortical incision was deepened, multiple branches of the middle cerebral artery were clipped and divided and a similar procedure was performed medially through the cingulate gyrus. The frontal lobe and AVM were ultimately excised and hemostasis was achieved. Estimated blood loss for the procedure was about 4000 cc and the patient received 6 U of packed red blood cells. Following reversal of anesthesia, the patient awakened without problems and remained only mildly lethargic for the next several days. Postoperative cerebral angiography (Fig. 2E) documented complete AVM removal. Case 7

This 30-year-old Ethiopian woman presented 18 months prior to admission with an SAH from a left frontal AVM. Prior to embolization of the lesion, she suffered a second SAH. At that time, she was discovered to have an aneurysm of the posterior carotid artery wall on the left. She underwent craniotomy and clipping of the aneurysm and, following an uneventful postoperative course, she returned to the hospital for treatment of her AVM. On September 18, 1989, the patient was brought to the angiography suite for her first procedure. Following baseline angiography, the anterior cerebral artery was catheterized. During attempted catheterization of a distal callosomarginal artery feeder, as the catheter was negotiating a right-angle bend, the patient complained of a severe increase in her headache. On test injection, intravascular contrast medium was revealed and some static medium was seen in the interhemispheric fissure. She was immediately given 50 mg protamine intravenously and four coils, 1 cm in length and curving in a 3-mm diameter, were rapidly placed into the vessel. She remained stable, with some flow through the coils. Approximately 1 to 1.5 mm of PVA particles were introduced between coils. The patient's headache stabilized and she did not lose consciousness, exhibit seizures, or develop a focal neurological deficit. The procedure was terminated at that point, and a CT scan was obtained (Fig. 3A—D). Subsequently, the patient underwent two more pro208

cedures, involving the pericallosal artery and three branches of the left middle cerebral artery. The most posterior middle cerebral artery branch was catheterized (Fig. 3E) but, on injection of 80 mg sodium Amytal (amobarbital), she developed a right facial droop. We elected not to embolize that branch, and an arteriogram was obtained at the end of embolization (Fig. 3F). Two weeks later, repeat angiography was thought to show some increase in the cloud of perforating branches arising from the distal, nonembolized middle cerebral artery branch. On October 30, 1989, the patient was taken to the operating room for resection, at which time one coil could be seen protruding through the wall of the callosomarginal artery, partly intravascular and partly extravascular. Surgery was complicated by the development of uncontrollable cerebral edema attributed to normal perfusion pressure breakthrough, unrelated to the embolization or its complication. Results The overall series is summarized in Table 1. Two of the surgical interventions (in Cases 1 and 2) were for vascular perforations at the time of embolization. With current technology, we might manage these interventionally today, as in Case 7. Case 3 represents intraparenchymal hemorrhage following rupture of the middle cerebral artery during inflation of a detachable balloon. That patient died. Cases 4 and 5 represent delayed intraparenchymal hemorrhage, accompanied by clot and mass effect. Other than Case 7 (presented above), the only patient not operated on (Case 6) was managed conservatively. She developed intraventricular hemorrhage following each of her two embolization procedures. Her ultimate neurological outcome was poor. Discussion Causes for Bleeds

We have identified two primary categories of hemorrhage: immediate and delayed. In our experience, the immediate hemorrhage is more likely to be caused by the catheterization or embolization process (vascular perforation or rupture). The delayed hemorrhage is more likely to be a hemorrhage into the malformation. Although the mechanism of hemorrhage following embolization of an AVM has not been studied directly, it is known that the pressure in arteries feeding an AVM rises as a result of embolization. 8 We observed that phenomenon while obtaining pressure measurements during the second embolization in Case 6. If the malformation is incompletely embolized, residual feeders may be confronted with arterial pressures not previously encountered. It is also known that substantial redistribution of cerebral blood flow into adjacent brain regions occurs coincident with embolization as portions of the shunt are eliminated.' Additionally, if the AVM is nearly obliterated, this can create stasis in dilated venous drainage which could lead to venous thrombosis J. Neurosurg / Volume 74 / February, 1991

Hemorrhage from interventional embolization

FIG. 3. Case 7. A: Angiogram showing a left frontal arteriovenous malformation. B: Test injection during catheterization of the callosomarginal artery for embolization revealing partial extravasation of contrast medium (arrovi) associated with increased headache. C: Arteriogram following placement of four 3-mm coils in the callosomarginal artery showing occlusion of that vessel (arrow). D: Computerized tomography scan showing a mixture of contrast medium and blood in the interhemispheric fissure (arrow). E: Angiogram showing catheterization of the most posterior middle cerebral artery branch. F: Angiogram showing the final postembolization status. At surgery a coil was seen protruding through a hole in the callosomarginal artery'.

and, again, raise the pressure confronting residual arterial feeders, as we saw in Case 4. Although it is possible that direct venous obstruction could occur with embolization using PVA particles, we doubt that this is a significant factor, since any particles small enough to

TABLE 1 Summary of hemorrhage after embolization of AVM's* Case

Location

Size of

No.

of AVM

AVM (cm)

1 2 3 4 5 6 7

frontal frontal perisylviant cerebellar frontal callosal frontal

3 3 3 1.7 5.5 5 5

Time of

Bleed

Embolic

immediate immediate delayed delayed delayed immediate

Surgical

Material Treatment

immediate none none B

PVA PVA, C PVA PVA, C

yes yes yes yes yes yes

no

* AVM = arteriovenous malformation; none = bled prior to embolization; B = detachable balloons; PVA = polyvinyl alcohol particles; C = platinum microcoils. t Perisylvian, frontal and insular.

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wash through the AVM should be carried even further distally in the larger veins. This is in contradistinction to glue, which can polymerize in situ in veins and would seem more likely to result in venous obstruction. We believe the venous thrombosis seen in our Case 4 was secondary to stasis caused by substantial obliteration of the AVM, which slowed flow in the enlarged venous channels, rather than due to direct obstruction by embolic material. Further study of this phenomenon is needed in order to understand the pathophysiology. Use of Heparin The use of heparin during embolization is controversial. Although it limits clot formation on the catheter or between the catheters in the coaxial system, one might argue that it increases the propensity to hemorrhagic complication. In our series, the three incidences of parenchymal or intraventricular bleeds all occurred hours or days following the procedure and were unrelated to heparinization. The arterial rupture that occurred during balloon inflation was lethal with

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P. D. Purdy, H. H. Batjer, and D. Samson or without heparinization. The other three were arterial perforations by the catheter, and one might argue that the heparin was potentially harmful. All three patients had good outcomes from their hemorrhages and suffered no neurological injury. Therefore, at least in our cases, the presence of heparin has not seemed injurious and we continue to use it.

Management of Bleeds Hemorrhagic events represent the most life-threatening of the complications associated with embolization of AVM's. In our series of 63 patients, hemorrhage occurred in a total of seven cases, with four good (neurologically intact) and three poor outcomes. Therefore, hemorrhagic complications with poor outcome occurred in 5% of our overall series. Potential approaches include: I ) conservative management without immediate radiological or surgical intervention; 2) immediate radiological intervention; and 3) immediate surgical intervention. Choice of therapy depends, to some extent, on the timing and etiology of the hemorrhage, as implied in the Results section. If the hemorrhage is of the immediate type, our experience has indicated that it probably relates to the catheterization process, is more likely to be an SAH, and may be controllable via embolic means. A delayed hemorrhage is probably caused from ruptured vessels within the malformation and is more likely to be accompanied by parenchymal clot. Our single exception was the patient with intraventricular hemorrhage (Case 6). We do not know whether other embolic materials would increase or decrease the likelihood of parenchymal hemorrhage at the time of embolization or later. As shown by these cases, immediate surgical intervention can yield gratifying outcomes in potentially catastrophic situations. This is especially true when the hemorrhage occurs hours after the catheter is removed, thus preventing immediate vascular occlusion via interventional means. One of our poor outcomes (Case 3) was associated with a technique (balloon occlusion) which we have subsequently abandoned. Another poor outcome resulted from failure to intervene immediately when the patient presented with headache and, in retrospect, CT evidence of venous thrombosis. The third patient with a poor outcome may have been improved with aggressive surgical intervention rather than conservative management. In three of the favorable outcomes, immediate surgical intervention with removal of the malformation was undertaken when the complication arose. In the fourth favorable outcome, the hemorrhage was controlled immediately via interventional techniques. Since a delayed hemorrhage is often associated with hematoma, surgical intervention allows evacuation of the mass in addition to control of the bleed. The three cases of anterior cerebral artery perforation illustrate the prudence, on occasion, of resisting the temptation to withdraw a catheter immediately when a complication is encountered. In these cases, the catheter 210

occluded the perforation of the artery and its withdrawal in a heparinized patient could have resulted in worse SAH. When possible during catheterization, we now advance the wire further from the tip of the Tracker catheter to prevent stiffening of the wire by the catheter. The wires are also now constructed with more flexible distal segments. However, the technique should still not be used casually by those inexperienced or without experienced supervision. Perforation can still occur with newer devices and wires, as demonstrated in Case 7. It is our opinion that the situation represented by a hemorrhagic complication of embolization in the presence of an AVM is unstable and cannot reliably be managed conservatively, especially when accompanied by intraparenchymal hematoma. If it can be managed interventionally, as in Case 7, the crisis can be aborted; if not, it should be considered a surgical emergency. The situation represented by venous thrombosis without hemorrhage is less clear. We now use MR imaging to help in that assessment. We choose early surgery in situations where severe stasis is noted after embolization and where we believe there is serious risk of venous thrombosis. We would press for urgent surgery if definite thrombosis were seen, although we have not encountered acute thrombosis since Case 7. In situations involving an AVM considered unresectable, the risk imposed by the potential for hemorrhage must be weighed in the decision to undertake primary embolic therapy. This experience has reinforced the value of a cohesive team effort with interdisciplinary participation in the decision-making process, beginning at the time of diagnostic studies. Well thought-out strategies regarding the specific goal of sequential embolization procedures as well as vigilance by the neurosurgical and neuroanesthetic teams on the days of planned interventional approaches offer the patient the best chance of achieving a successful outcome when unusual but unavoidable life-threatening hemorrhagic complications develop. Acknowledgment The authors wish to acknowledge Leslie Mihal for her assistance in the preparation of this manuscript. References 1. Andrews BT, Wilson CB: Staged treatment of arteriovenous malformations of the brain. Neurosurgery 21: 314-323, 1987 2. Batjer HH, Purdy PD, Giller CA, et al: Evidence of redistribution of cerebral blood flow during treatment of intracranial arteriovenous malformation. Neurosurgery 25:599-605, 1989 3. Berenstein AB, Krall R, Choi IS: Embolization with nbutyl-cyanoacrylate in the management of CNS vascular lesions. AJNR 10:883, 1989 (Abstract) 4. Dion JE, Vinuela IV, Lylyk P, et al: Ivalon-33% ethanolavitene embolic mixture: clinical experience with neuroradiological endovascular therapy in 40 arteriovenous malformations. AJNR 9:1029-1030, 1988 (Abstract) .1. Neurosurg. Volume 74 / February, 1991

Hemorrhage from interventional embolization 5. Eskridge JM, Hartling RP: Preoperative embolization of brain AVMs using surgical silk and polyvinyl alcohol. AJNR 10:882. 1989 (Abstract) 6. Fox AJ, Girvin JP, Vilitiela F. et al: Rolandic arteriovenous malformations: improvement in limb function by IBC embolization. AJNR 6:575-582, 1985 7. Hilal SK, Khandji AG, Chi TL, et al: Synthetic fibercoated platinum coils successfully used for the endovascular treatment of arteriovenous malformations, aneurysms and direct arteriovenous fistulas of the CNS. AJNR 9:1030, 1988 (Abstract) 8. Jungreis CA, Horton JA, Hecht ST: Blood pressure changes in feeders to cerebral arteriovenous malformations during therapeutic embolization. AJNR 10: 575-577, 1989 9. Kerber C: Intracranial cyanoacrylate: a new catheter therapy for arteriovenous malformation. Invest Radio' 10: 536-537, 1975 (Letter) 10. Kerber CW: Balloon catheter with a calibrated leak. Radiology 120:547-550, 1976 11. Lasjaunias P, Manelfe C, Ter Brugge K, et al: Endovascular treatment of cerebral arteriovenous malformations. Neurosurg Rev 9:265-275, 1986 12. Pelz DM, Fox AJ, Vinuela F, et al: Preoperative embolization of brain AVMs with isobutyl-2-cyanoacrylate. AJNR 9:757-764, 1988

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13. Purdy PD, Samson D, Batjer HH, et al: Preoperative embolization of cerebral arteriovenous malformations with polyvinyl alcohol particles: experience in 51 adults. AJNR 11:501-510, 1990 14. Samson D. Ditmore QM, Beyer CW Jr: Intravascular use of isobutyl-2-cyanoacrylate: Part 1. Treatment of intracranial arteriovenous malformations. Neurosurgery 8: 43-51, 1981 15. Spetzler RF„ Martin NA, Carter LP, et al: Surgical management of large AVM's by staged embolization and operative excision. J Neurosurg 67:17-28, 1987 16. Stein BM, Wolpert SM: Surgical and embolic treatment of cerebral arteriovenous malformations. Surg Neurol 7: 359-369, 1977 17. Tadavarthy SM, Moller JH, Amplatz K: Polyvinyl alcohol (Ivalon) — a new embolic material. AJR 125:609-616, 1975

Manuscript received January 5, 1990. Accepted in final form July 16, 1990. Address reprint requests to: Phillip Purdy, M.D., Department of Radiology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, Texas 75235.

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