Treatment decisions for patients with brain arteriovenous

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1 Risk of Endovascular Treatment of Brain Arteriovenous Malformations A. Hartmann, MD; J. Pile-Spellman, MD; C. Stapf, MD; R.R. Sciacca, EngScD; A. Faulstich, MS; J.P. Mohr, MD; H.C. Schumacher, MD; H. Mast, MD Background and Purpose Independently assessed data on frequency, severity, and determinants of neurological deficits after endovascular treatment of brain arteriovenous malformations (AVMs) are scarce. Methods From the prospective Columbia AVM Study Project, 233 consecutive patients with brain AVM receiving 1 endovascular treatments were analyzed. Neurological impairment was assessed by a neurologist using the Scale before and after completed endovascular therapy. Multivariate logistic regression models were used to identify demographic, clinical, and morphological predictors of treatment-related neurological deficits. The analysis included the components used in the Spetzler-Martin risk score for AVM surgery (AVM size, venous drainage pattern, and eloquence of AVM location). Results The 233 patients were treated with 545 endovascular procedures. Mean follow-up time was 9.6 months (SD, 18.1 months). Two hundred patients (86%) experienced no change in neurological status after treatment, and 33 patients (14%) showed treatment-related neurological deficits. Of the latter, 5 (2%) had persistent disabling deficits ( score 2), and 2 (1%) died. Increasing patient age [odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01 to 1.08], number of embolizations (OR, 1.41; 95% CI, 1.16 to 1.70), and absence of a pretreatment neurological deficit (OR, 4.55; 95% CI, 1.03 to 20.0) were associated with new neurological deficits. None of the morphological AVM characteristics tested predicted treatment complications. Conclusions From independent neurological assessment and prospective data collection, our findings suggest a low rate of disabling treatment complications in this center for endovascular brain AVM treatment. Risk predictors for endovascular treatment differ from those for AVM surgery. (Stroke. 2002;33: ) Key Words: arteriovenous malformations embolization, therapeutic outcome Treatment decisions for patients with brain arteriovenous malformations (AVMs) are based on natural-course risk estimates weighed against outcome data from invasive intervention. At present, both remain incompletely defined. 1 4 Endovascular treatment of brain AVMs aims to obliterate or reduce the size of the malformation. It is frequently followed by surgical AVM removal or radiotherapy. 5 7 As with AVM surgery, determinants of complications from endovascular treatment are not well described Originally designed to predict outcome from AVM surgery, the Spetzler-Martin 12 grading system is often used to categorize brain AVMs before endovascular therapy as well, but its applicability to this treatment modality remains unsettled. Studies on AVM embolization outcome using independent neurological data collection are scarce. The purpose of this single-center study was to prospectively and independently assess treatment outcome after embolization therapy of brain AVMs with modern embolization techniques and to analyze determinants of treatment-related neurological deficits. Patients and Methods The New York (NY) AVM Databank is an ongoing, prospective database collecting demographic, clinical, morphological, and treatment data on consecutive patients admitted to the New York Presbyterian Hospital with brain AVM proven by brain imaging and conventional cerebral angiography. Other types of intracranial fistulas (eg, dural AV fistulas, vein of Galen type malformations) are not included. Study patients are drawn from the New York metropolitan area and from distant referral sites. Further details on the design and methods of the data set have been described in prior publications. 3,5,13 As a general rule, the study patients were treated with the goal of complete AVM obliteration or removal by endovascular occlusion alone or in combination with subsequent surgery or radiosurgery. The 233 consecutive patients with brain AVMs receiving 1 endovascular treatments between 1991 and 1998 were analyzed. Subsequent treatment was surgical in 130 patients (56%) and Received January 7, 2002; final revision received April 1, 2002; accepted April 8, From the Stroke Center, Neurological Institute, New York Presbyterian Hospital, New York (A.H., C.S., R.R.S., J.P.M., H.C.S., H.M.); Department of Interventional Neuroradiology, Columbia University, College of Physicians and Surgeons, New York, NY (A.H., J.P.-S.); Stroke Unit, Department of Neurology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany (A.H., C.S.); and Schlaganfallzentrum Halle, Stroke Unit, Berufsgenossenschaftliche Kliniken, Bergmannstrost, Halle, Germany (A.F., H.C.S., H.M.). Correspondence to Andreas Hartmann, MD, Stroke Unit, Neurologische Klinik, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, 1200 Berlin, Germany. ahart@zedat.fu-berlin.de 2002 American Heart Association, Inc. Stroke is available at DOI: /01.STR B2 1816

2 Hartmann et al Brain AVM Embolization Outcome 1817 radiosurgical in 23 patients (10%). Neurological deficit, disability, and impairment were independently assessed by a study neurologist. Functional neurological status was documented before embolization and after each endovascular treatment session until completion of endovascular therapy by use of the modified Scale. 14,15 Any worsening of the patient s preembolization score was coded as a new neurological deficit. This included worsening of patients with a preexisting neurological deficit. New neurological deficits were classified as disabling when scores were 3. For patients with baseline scores of 2, any score increase was classified as disabling. Superselective microcatheter cannulation of arteries feeding the AVM and injection of N-butyl cyanoacrylate were used to occlude the fistulae. The technique remained the same throughout the study period. One hundred patients were embolized with 1 session each; 133 patients were treated multiple times (mean, 2.4 procedures; SD, 2.8 procedures; range, 1 to 11 procedures). Univariate statistics ( 2 or, when appropriate, Fisher s exact test, t test) and forward stepwise multiple logistic regression procedures were used to describe the effect of demographic factors, mode of initial AVM presentation, preembolization neurological status, and morphological parameters on embolization outcome. To test the validity of the Spetzler-Martin grading system, the univariate and multivariate (backward stepwise multiple logistic regression procedures) analyses included the total score from the grading system and its individual components: AVM size (score of 1 small size, with a maximum diameter of 3 cm; 2 medium size, with a diameter of 3 to 6 cm; 3 large size, with a diameter of 6 cm), venous drainage (score of 1 AVM with any drainage into the internal, deep cerebral venous system), and location of the AVM (score of 1 for AVM in functionally important, so-called eloquent brain regions: the sensorimotor, language, and visual cortex; hypothalamus and thalamus; internal capsule; brainstem; cerebellar peduncles; and deep cerebellar nuclei). Results Demographic, clinical, and morphological information on the study sample is given in Table 1. By baseline score, 89% of the patients had no functionally relevant neurological deficit ( score 0 or 1), and 94% were nondisabled ( score 2; Table 2). A total of 33 patients [14%; 95% confidence interval (CI), 9 to 19] showed treatment-related new neurological deficits, including 5 with disabling deficits (2%; 95% CI, 0 to 4) and 2 (1%; 95% CI, 0 to 2) who died. By scale, 200 patients (86%; 95% CI, 81 to 91) experienced no change in neurological status after treatment, and 92% were nondisabled (Table 2). Of the 200 patients who experienced no change in functional status, 41 (18%) had a preexisting neurological deficit that remained unchanged after endovascular therapy. After the embolization session that caused a new neurological deficit, 19 of 33 patients (58%) later underwent surgery, 9 (27%) continued with the embolization therapy, 3 (9%) had achieved complete AVM obliteration at the time of the complication, and 2 (6%) died without receiving further invasive treatment. The 2 patients who died suffered parenchymal hemorrhage, both with ventricular extension. The 5 patients with disabling complications had treatment-induced ischemic strokes (2 middle cerebral artery, 1 anterior choroidal artery, 1 anterior inferior cerebellar artery, and 1 superior cerebellar artery infarct). Clinical information on these patients is provided in Table 3. Patients with a treatment-related new neurological deficit had significantly more embolizations and were more frequently neurologically normal at baseline (Table 4). TABLE 1. Demographic, Clinical, and Morphological Characteristics of 233 Patients With Brain AVM Undergoing Embolization Therapy Mean SD age (range), y (9 72) Female sex, n (%) 124 (53) Initial presentation, n (%) Intracranial hemorrhage 93 (40) Seizure 74 (32) Headache 40 (17) Focal deficit 11 (5) Other/asymptomatic 15 (6) Embolizations, n 545 Mean SD follow-up time, mo Patients undergoing surgery after endovascular treatment, n (%) 126 (54) Maximum (mean SD) AVM diameter (range), mm (5 80) AVMs with deep arterial feeders,* n (%) 42 (18) AVMs with choroidal arterial feeders, n (%) 49 (21) Border-zone AVM location, n (%) 124 (53) Patients with concurrent arterial aneurysms, n (%) 41 (18) Spetzler-Martin criteria, n (%) Small AVM (diameter 3 cm) 46 (20) Medium AVM (3 6 cm) 179 (77) Large AVM ( 6 cm) 8 (3) Deep venous drainage, n (%) 128 (55) Eloquent location, n (%) 159 (68) Spetzler-Martin score, n (%) 1 12 (5) 2 43 (19) (43) 4 68 (29) 5 8 (3) *Defined as penetrating branches of the major intracranial arteries of the circle of Willis. Defined as arterial supply by branches of 2 of the major arteries of circle of Willis. Includes aneurysms on feeding arteries and intranidal aneurysms. Includes location in the sensorimotor, visual, or language cortex; basal ganglia; internal capsule; brainstem; cerebellar peduncles; and deep cerebellar nuclei. In the multivariate analyses, increasing age, number of embolizations, and normal neurological status at baseline were significantly associated with treatment complications (Table 5). For all other variables shown in Table 4, no significant association was found. Neither the overall score of the Spetzler-Martin grading system (P 0.163) nor its 3 components tested separately predicted treatment outcome (Table 6). Restricting the univariate analysis to disabling neurological deficits or death, we found significant associations for increasing age [P 0.021; odds ratio (OR), 5.59; 95% CI, 1.11 to 28.14], initial presentation with hemorrhage (P 0.017; OR, 9.59; 95% CI, 1.14 to 80.98), small AVM size (P 0.005; OR, 5.30; 95% CI, 1.13 to 24.95), and presence of deep arterial feeders (P 0.021; OR, 6.60; 95% CI, 1.42 to 30.68). Of the 7 patients (43%) with disabling complications

3 1818 Stroke July 2002 TABLE 2. Scores of 233 Patients Undergoing Endovascular Brain AVM Treatment Before and After Completed Embolization Therapy Baseline Posttreatment Score* n % n % * 0 no symptoms at all; 1 able to carry out all usual duties and activities; 2 unable to carry out all previous activities but able to look after own affairs; 3 requiring some help but able to walk without assistance; 4 unable to walk without assistance and unable to attend to bodily needs; 5 bedridden, incontinent, and requiring constant nursing care and attention; and 6 death. or fatal outcome, 3 had small AVMs (maximum diameter 30 mm according to Spetzler-Martin criteria). Of these, 1 was located in the cerebellar hemisphere, another in the brainstem, and the last in the basal ganglia. The low number of end points precluded meaningful multivariate models for disabling deficits or death. Additional partial correlation analyses showed that younger patients carried larger AVMs and were treated more often than older patients. TABLE 3. Patient Sex Discussion Outcome after AVM embolization therapy has improved over the last decade. The rate of treatment-related permanent neurological deficits and death culled from the literature ranges from 4% to 18%, 5 depending on the material used to obliterate the malformation, the means of delivering the occlusive agent, and patient selection. 9,10,16 19 Our data suggest a further reduction in treatment-related disabling morbidity and mortality. However, despite the low number of disabling complications, the overall rate of neurological deficits was 14%. Prospective and independent evaluation by a neurologist may reveal a larger number of less severe complications, as has been shown in carotid surgery outcome studies. 20,21 Consequently, the detection rate of mild neurological deficits may have been higher in our study than in others, but the low rate of disabling complications is accredited. The 2 fatal complications in our series were brain hemorrhages. There was no intranidal aneurysm in either patient, and the flow-related aneurysm found in 1 patient was not considered a likely source of the hemorrhage. Also, no venous occlusion that may have led to outflow obstruction with subsequent hemorrhage was noted during or after the embolization. Autopsy was not performed in either patient; therefore, the cause of hemorrhage remains undetermined. Some authors have suggested that most complications from embolization occur on the venous side of the AVM, 6 but in our series, all nonhemorrhagic disabling events were due to arterial occlusions. In our findings, the number of embolizations and a normal neurological status before treatment were significant predictors of treatment-related neurological deficits. The increasing risk with additional embolizations is not surprising, given the greater exposure to potential complications with each treatment. The complication risk from embolization therefore is likely to be higher in patients whose treatment plan includes multiple embolization sessions. Normal neurological examination at baseline as a predictor of treatment-related deficits may reflect the higher likelihood of patients with no preexisting focal neurological signs to reveal new symptoms, especially a better detection rate for mild deficits. A similar effect has been observed in surgical AVM treatment, 8 lending support to our observation in this study. Clinical Status of Patients With Brain AVMs and Endovascular Treatment-Related Disabling Deficits or Death Age, y Clinical Presentation AVM Location 1 M 20 Hemorrhage Left frontotemporo-parietal Deep Arterial Feeders Aneurysms Venous Drainage Embolizations, n Preembolization Postembolization Clinical Syndrome None None Deep AChA infarct with moderate hemiparesis 2 M 53 Hemorrhage Left occipital MCA Flow related Deep superficial Massive ventricular hemorrhage; patient died 3 F 50 Seizure Left fronto-temporal MCA None Superficial MCA infarct with aphasia and moderate hemiparesis 4 M 62 Hemorrhage Left frontal ACA None Deep superficial MCA infarct with moderate hemiparesis; myocardial infarction 5 M 52 Hemorrhage Brainstem BA None Deep superficial AICA infarct with dysarthria and ataxia 6 M 30 Hemorrhage Left basal ganglia PChA None Deep Thalamic and ventricular hemorrhage; patient died 7 M 67 Hemorrhage Left cerebellar AICA Flow related Superficial SCA infarct with ataxia AChA indicates anterior choroidal artery; MCA, middle cerebral artery; ACA, anterior cerebral artery; BA, basilar artery; AICA, anterior inferior cerebellar artery; PChA, posterior choroidal artery; and SCA, superior cerebellar artery.

4 Hartmann et al Brain AVM Embolization Outcome 1819 TABLE 4. Association of Demographic and Morphological Parameters With Neurological Complications Related to Endovascular AVM Treatment in 233 Patients Postembolization Outcome Any Deficit No Deficit Parameter (n 33) (n 200) OR (95% CI) P Age (mean SD), y ( ) Female sex (n 124), n (%) 14 (42) 110 (55) 0.60 ( ) Embolizations (mean SD), n ( ) 0.005* No neurological deficit at baseline (n 185), n (%) 31 (94) 154 (77) 4.63 ( ) 0.026* Mode of initial presentation, n (%) Hemorrhage (n 93) 14 (42) 79 (40) 1.13 ( ) Seizure (n 74) 9 (27) 65 (33) 0.78 ( ) Headache (n 40) 7 (21) 33 (17) 1.36 ( ) Neurological deficit (n 11) 1 (3) 10 (5) 0.59 ( ) Other/asymptomatic (n 15) 2 (6) 13 (7) 0.93 ( ) Maximum AVM diameter (mean SD), mm ( ) Infratentorial AVM location (n 24), n (%) 2 (6) 22 (11) 0.52 ( ) Border-zone location (n 124), n (%) 17 (52) 107 (54) 0.92 ( ) Deep arterial feeders (n 42), n (%) 9 (27) 33 (17) 1.89 ( ) Choroidal arterial feeders (n 49), n (%) 9 (27) 40 (20) 1.50 ( ) Concurrent aneurysms, n (%) Any (n 43) 6 (18) 37 (19) 0.98 ( ) Flow related (n 33) 5 (15) 28 (14) 1.10 ( ) Intranidal (n 10) 1 (3) 9 (5) 0.66 ( ) Spetzler-Martin criteria, n (%) Small AVM size ( 3 cm) 5 (15) 42 (21) 0.67 ( ) Medium AVM size (3 6 cm) 27 (82) 151 (76) 1.46 ( ) Large AVM size ( 6 cm) 1 (3) 7 (4) 0.86 ( ) Deep venous drainage, n (%) 22 (67) 107 (54) 1.74 ( ) Eloquent AVM location# 24 (73) 136 (68) 1.26 ( ) Percentages refer to column total. *P Tested for significance with 2 statistics or Fisher s exact test when appropriate unless otherwise indicated. Tested for significance with t test statistics. Defined as arterial supply by branches of 2 of the major arteries of the circle of Willis. Defined as penetrating branches of the major intracranial arteries of the circle of Willis. Includes aneurysms related to shunt flow and intranidal aneurysms. #Includes location in the visual, language, and sensorimotor cortex; basal ganglia; internal capsule; brainstem cerebellar peduncles; and deep cerebellar nuclei. The reason for the higher treatment risk in older patients despite their smaller AVMs and less frequent embolizations than younger patients is less obvious. General vascular disease may be more prevalent in older patients, although TABLE 5. Multivariate Logistic Regression Model Testing the Association of Demographic and Morphological Parameters With Neurological Deficits Related to Endovascular AVM Treatment in 233 Patients Parameter OR 95% CI P Age Number of embolizations* No neurological deficit at baseline *Defined as sessions of endovascular treatment regardless of the number of vessels occluded at each session. none of the patients treated showed evidence of atherosclerosis. Moreover, the effect of age was marginal (OR, 1.04; lower limit of the CI, 1.01); the mean age difference between TABLE 6. Multivariate Logistic Regression Model Testing the Association of Spetzler-Martin Score and Its Components With Neurological Deficits Related to Endovascular AVM Treatment in 233 Patients Parameter OR 95% CI P Spetzler-Martin score Spetzler-Martin components AVM size Deep venous drainage Eloquent AVM location

5 1820 Stroke July 2002 the patients who developed new deficits and those who remained unchanged was small (40 14 versus years); and changes in hemostasis 22 or nutritional problems encountered in surgery on elderly patients 23 did not apply to our patients. The low rate of disabling complications or death in our study precludes a meaningful multivariate analysis of their predictors. Trends from our univariate analyses suggest clinical and morphological predictors of poor embolization outcome that were also identified in natural-course risk estimates, ie, hemorrhage at initial presentation and small AVM size. 3 The association of deep arterial feeders with the failure to achieve complete obliteration of the malformation was previously suggested. 24 However, the CIs of our relative risk analyses were large, and studies on more patients are needed to better define predictors of complications. In our analysis, neither the total score of the Spetzler- Martin grading system nor any of its 3 components predicted treatment complications. The system was originally designed and validated to predict surgical treatment outcome. 12,25 Although found helpful by many authors, our results suggest that morphological variables other than those in the grading system need to be defined to predict outcome from endovascular therapy. It remains unproven whether endovascular AVM treatment affects the complication risk from subsequent surgery or radiosurgery. Ideally, embolization facilitates other modes of treatment, and a prior analysis showed no deleterious effect of endovascular therapy on AVM surgery outcome. 8 In staged AVM treatment, complications from all treatment forms need to be considered in determinations of the total complication rate for complete AVM removal. Acknowledgment This work was supported in part by NIH grant RO1 NS (principal investigator, W.L. Young, MD). References 1. Fisher WS. Therapy of AVMs: a decision analysis. Clin Neurosurg. 1995;42: Ondra SL, Troupp H, George ED, Schwab K. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg. 1990;73: Mast H, Young WL, Koennecke HC, Sciacca RR, Osipov A, Pile- Spellman J, Hacein-Bey L, Duong H, Stein BM, Mohr JP. Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet. 1997;350: Duong DH, Young WL, Vang MC, Sciacca RR, Mast H, Koennecke HC, Hartmann A, Joshi S, Mohr JP, Pile-Spellman J. Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations. Stroke. 1998;29: Arteriovenous Malformation Study Group. Arteriovenous malformations of the brain in adults. N Engl J Med. 1999;340: Berenstein A, Lasjaunias P. Endovascular treatment of cerebral lesions. In: Berenstein A, Lasjaunias P, eds. Surgical Neuroangiography. New York, NY: Springer Verlag; Jafar JJ, Davis AJ, Berenstein A, Choi IS, Kupersmith MJ. The effect of embolization with N-butyl cyanoacrylate prior to surgical resection of cerebral arteriovenous malformations. J Neurosurg. 1993;78: Hartmann A, Stapf C, Hofmeister C, Mohr JP, Sciacca RR, Stein BM, Faulstich A, Mast H. Determinants of neurological outcome after surgery for brain arteriovenous malformation. Stroke. 2000;31: Gobin YP, Laurent A, Merienne L, Schlienger M, Aymard A, Houdart E, Casasco A, Lefkopoulos D, George B, Merland JJ. Treatment of brain arteriovenous malformations by embolization and radiosurgery. J Neurosurg. 1996;85: Vinuela F, Dion JE, Duckwiler G, Martin NA, Lylyk P, Fox A, Pelz D, Drake CG, Girvin JJ, Debrun G. Combined endovascular embolization and surgery in the management of cerebral arteriovenous malformations: experience with 101 cases. J Neurosurg. 1991;75: Mast H, Koennecke HC, Meisel J, Osipov A, Hartmann A, Lasjaunias P, Pile-Spellman J, Hacein-Bey L, Young WL, Mohr JP. Zur Therapie zerebraler arteriovenöser Malformationen. Nervenarzt. 1998;69: Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986;65: Hartmann A, Mast H, Mohr JP, Koennecke HC, Osipov A, Pile-Spellman J, Duong DH, Young WL. Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation. Stroke. 1998;29: van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19: de Haan R, Limburg M, Bossuyt P, van der MJ, Aaronson N. The clinical meaning of handicap grades after stroke. Stroke. 1995;26: Debrun G, Vinuela F, Fox A, Drake CG. Embolization of cerebral arteriovenous malformations with bucrylate. J Neurosurg. 1982;56: Purdy PD, Samson D, Batjer HH, Risser RC. Preoperative embolization of cerebral arteriovenous malformations with polyvinyl alcohol particles: experience in 51 adults. AJNR Am J Neuroradiol. 1990;11: Wikholm G, Lundqvist C, Svendsen P. Transarterial embolization of cerebral arteriovenous malformations: improvement of results with experience. AJNR Am J Neuroradiol. 1995;16: Paulsen RD, Steinberg GK, Norbash AM, Marcellus ML, Marks MP. Embolization of basal ganglia and thalamic arteriovenous malformations. Neurosurgery. 1999;44: ; discussion Rothwell PM, Slattery J, Warlow CP. A systematic review of the risks of stroke and death due to endarterectomy for symptomatic carotid stenosis. Stroke. 1996;27: Hartmann A, Hupp T, Koch HC, Dollinger P, Stapf C, Schmidt R, Hofmeister C, Thompson JL, Marx P, Mast H. Prospective study on the complication rate of carotid surgery. Cerebrovasc Dis. 1999;9: Boldt J, Huttner I, Suttner S, Kumle B, Piper SN, Berchthold G. Changes of haemostasis in patients undergoing major abdominal surgery: is there a difference between elderly and younger patients? Br J Anaesth. 2001; 87: Bozzetti F. Surgery in the elderly: the role of nutritional support. Clin Nutr. 2001;20: Wikholm G, Lundqvist C, Svendsen P. Embolization of cerebral arteriovenous malformations, part I: technique, morphology, and complications. Neurosurgery. 1996;39: ; discussion Hamilton MG, Spetzler RF. The prospective application of a grading system for arteriovenous malformations. Neurosurgery. 1994;34:2 6; discussion Deruty R, Pelissou-Guyotat I, Amat D, Mottolese C, Bascoulergue Y, Turjman F, Gerard JP. Complications after multidisciplinary treatment of cerebral arteriovenous malformations. Acta Neurochir (Wien). 1996;138: Steinberg GK, Lane B, Marks MP. Endovascular therapy for intracranial vascular lesions. West J Med. 1990;153: Henkes H, Nahser HC, Berg-Dammer E, Weber W, Lange S, Kuhne D. Endovascular therapy of brain AVMs prior to radiosurgery. Neurol Res. 1998;20: