Acta Neurochir DOI 10.1007/s00701-015-2477-6
LETTER TO THE EDITOR - EDITORIAL
Treatment of unruptured brain AVM in the aftermath of ARUBA and the Scottish Audit of Intracranial Vascular Malformations Hans-Jakob Steiger 1,3 & Karl Schaller 2
Received: 5 June 2015 / Accepted: 8 June 2015 # Springer-Verlag Wien 2015
We appreciate the thoughtful comments of T.R. Meling and the support of a constructive strategy regarding unruptured brain AVM. The results of the ARUBA trial have been widely commented on and the weaknesses of the study have been pointed out, i.e., the lack of differentiation between Spetzler–Martin grades and treatment modalities, and the fact that the effect of microsurgical removal was not assessed by the study design [4, 8, 9]. The report of the Scottish Audit of Intracranial Vascular Malformations drew less attention, but provided essentially the same result that intervention led to a worse outcome compared to the natural history [1]. The results of ARUBA and the Scottish Audit of Intracranial Vascular Malformations showed an almost identical pattern of strokes following intervention, with initially a higher rate of events than in untreated patients and secondary regression to the rate of the natural history. Therefore, we have to accept that the way we have been treating unruptured AVM was not right and needs correction. As pointed out by Meling, the treatment-associated morbidity rates as given in the ARUBA trial, and also the Scottish Audit, are very different from the rates given in microsurgical series. The high morbidity rates of ARUBA and the Scottish Audit are the footprint of destabilized and incompletely eliminated AVM, i.e., the pattern of endovascular embolization
* Hans-Jakob Steiger [email protected] 1
Department of Neurosurgery, Heinrich-Heine-Universität, Düsseldorf, Germany
2
Department of Neurosurgery, Hôpital Universitaire de Genève, Geneva, Switzerland
3
Neurochirurgische Klinik, Universitätsklinikum, Moorenstr 5, Geb. 10.54, 40225 Düsseldorf, Germany
[19]. Without any doubt, radiosurgery contributed to the continuing stroke rate in the interventional cohorts but was unlikely a major factor for the increased rate following intervention. Despite the obvious pattern of the delayed hemorrhages in the ARUBA and the Scottish Audit cohorts, questions remain. All non-randomized series provided rates of stroke after microsurgery, radiosurgery, and embolization far below the 9– 10 % per year rate of ARUBA and the Scottish Audit. Probability of hemorrhage after successful microsurgery appears, however, to be approximately one-tenth the rate after endovascular embolization, according to the meta-analysis of van Beijnum [19]. Although the numbers of hemorrhages given in nonrandomized series remain far below the incidence rates in ARUBA and the Scottish cohort, it appears likely that endovascular therapy was the primary factor for the exorbitant event rate following intervention. Analyzing all published series, van Beijnum and coworkers found reported annual hemorrhage rates of 0.18 % after microsurgery 1.7 % after stereotactic radiosurgery and 1.7 % after embolization. The obvious destabilizing effect resulting from treatment as seen in the ARUBA and Scottish Audit cohorts is hardly explainable by radiosurgery. Endovascular intranidal embolization emerged in the 1980s as a minimally invasive alternative to surgical elimination. It was soon realized, however, that complete elimination could not be routinely achieved. The introduction of Onyx, offering more controllable intranidal dispersion, did not change the picture fundamentally, achieving complete elimination in maximally 50 % [5, 13, 16]. Embolization also remained associated with substantial complications despite technical advances. The rate of resulting morbidity or death is given in most recent series in the range of 10 % [6, 13, 18]. Furthermore, the risk of incompletely embolized AVM remains unclear on the basis of monocentric series. Lasjaunias
Acta Neurochir
and collaborators suggested that partial occlusion still reduced the risk of hemorrhage [7]. This concept justified to continue relatively uncritically with embolization as a stand-alone therapy for ruptured and unruptured AVM. During recent years, however, there has been a silent retreat of endovascular therapy as a stand-alone management of brain AVM. While in 2014 almost 40 publications on stereotactic radiosurgery for AVM are listed in PubMed, some 20 on microsurgical resection, less than ten publications focus on endovascular treatment. In comparison, PubMed listed more than 20 publications on endovascular treatment in 2005, while reports on microsurgical resection were similar to 2014 and papers on stereotactic radiosurgery were less than 20. What remains is the supportive function of endovascular therapy prior to surgery. There is no doubt that endovascular therapy was a major technical advance in the treatment of high-grade AVM. The surgical case fatality rate for brain AVM was in the range of 15 % prior to introduction of endovascular therapy and has decreased to almost zero since [12, 19]. Complex Spetzler–Martin grade 3 and 4 AVMs (corresponding to the recently introduced Spetzler-Ponce classes B and C) have become manageable with the introduction of endovascular therapy as a preparatory adjunct for subsequent microsurgical removal [14]. Regarding presurgical embolization, surgeons have become more cautious. Endovascular embolization is not innocent. Published combined procedural morbidity and mortality rates are reported around 10 % also in the more recent series [2, 6, 13, 17, 18]. It is unclear whether the risk of subsequent surgical resection decreases correspondingly. Many of us have adopted a policy of routine embolization as the first step and reserving additional microsurgery or stereotactic radiosurgery in case of incomplete endovascular obliteration. Neurosurgeons were usually very willing to accept routine preoperative embolization due to its promise to render microsurgery easier and safer, but even this concept needs to be critically re-evaluated based on current evidence. Prior work by the group of one of us described surgical problems following arterial embolization with resulting congestion of the nidus [15], and Morgan and coworkers recently found no positive effect of preoperative embolization on surgical outcome [10]. Based on current evidence, endovascular embolization can therefore not be recommended as a preoperative adjunct for Spetzler–Martin grade 1 and 2 AVMs (corresponding to Spetzler-Ponce class A). Delayed obliteration of AVM following stereotactic radiosurgery contributed to the continuing stroke rate after intervention in the ARUBA trial and the Scottish Audit. Annual hemorrhage rates after radiosurgery have been reported on the average as 1.7 % [19], therefore not significantly accounting for the 9–10 % per year stroke rate during the first 4 years in the Scottish Audit and ARUBA. Nonetheless, the position of stereotactic radiosurgery remains open at the present time. ARUBA was not designed to grasp a potential benefit of this
mode of treatment because of the inherent latency of several years. A protective effect becoming visible only after several years must not necessarily be considered negative, as long as the complication rates remain low. Studies with a follow-up of 5–20 years will be required in order to judge the position of radiosurgery conclusively. The recent work of Bervini and colleagues, Nerva and colleagues, as well as the report in the current issue provide sufficient substance to recommend microsurgery to patients with unruptured AVM Spetzler–Martin grade 1 and 2 (corresponding to Spetzler-Ponce class A) [3, 11, 14, 16]. In contrast, treatment of unruptured Spetzler–Martin grade 3 and 4 AVMs needs to be seen critically. Here, any treatment appears to be as risky as or riskier than the natural history. It is important to consider microsurgical treatment of unruptured AVMs Spetzler–Martin grade 1 and 2 as a stand-alone therapy, as it has been recently proposed by Spetzler and his group and by other eminent neurovascular surgeons [10, 14]. Unruptured brain AVM present a substantial burden for patients with a 2.3 % annual risk of rupture resulting with 50 % chance in death or permanent disability. It is necessary, however, to continue microsurgical treatment within a controlled frame, at least with accurate book keeping, in order to obtain firm data regarding risks and benefits. Hans-Jakob Steiger, Düsseldorf Karl Schaller, Geneva
References 1.
Al-Shahi Salman R, White PM, Counsell CE, du Plessis J, van Beijnum J, Josephson CB, Wilkinson T, Wedderburn CJ, Chandy Z, St George EJ, Sellar RJ, Warlow CP, Scottish Audit of Intracranial Vascular Malformations Collaborators (2014) Outcome after conservative management or intervention for unruptured brain arteriovenous malformations. JAMA 311(16):1661–1669 2. Baharvahdat H, Blanc R, Termechi R, Pistocchi S, Bartolini B, Redjem H, Piotin M (2014) Hemorrhagic complications after endovascular treatment of cerebral arteriovenous malformations. AJNR Am J Neuroradiol 35(5):978–983 3. Bervini D, Morgan MK, Ritson EA, Heller G (2011) Surgery for unruptured arteriovenous malformations of the brain is better than conservative management for selected cases: a prospective cohort study. J Neurosurg 121(4):878–990 4. Elhammady MS, Heros RC, Editorial (2014) Management of incidental cerebral AVMs in the post-ARUBA era. J Neurosurg 121(5): 1011–1014 5. Jordan JA, Llibre JC, Vazquez F, Rodríguez RM (2014) Predictors of total obliteration in endovascular treatment of cerebral arteriovenous malformations. Neuroradiol J 27(1):108–114 6. Kim LJ, Albuquerque FC, Spetzler RF, McDougall CG (2006) Postembolization neurological deficits in cerebral arteriovenous malformations: stratification by arteriovenous malformation grade. Neurosurgery 59(1):53–9, discussion 53–59 7. Meisel HJ, Mansmann U, Alvarez H, Rodesch G, Brock M, Lasjaunias P (2002) Effect of partial targeted N-butyl-cyano-acrylate embolization in brain AVM. Acta Neurochir (Wien) 144(9): 879–887
Acta Neurochir 8.
9.
10.
11.
12.
13.
Meling TR, Proust F, Gruber A, Niemela M, Regli L, Roche PH, Vajkoczy P (2014) On apples, oranges, and ARUBA. Acta Neurochir (Wien) 156(9):1775–1779 Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, Al-Shahi Salman R, Vicaut E, Young WL, Houdart E, Cordonnier C, Stefani MA, Hartmann A, von Kummer R, Biondi A, Berkefeld J, Klijn CJ, Harkness K, Libman R, Barreau X, Moskowitz AJ, International ARUBA investigators (2014) Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 383(9917):614–621 Morgan MK, Davidson AS, Koustais S, Simons M, Ritson EA (2013) The failure of preoperative ethylene-vinyl alcohol copolymer embolization to improve outcomes in arteriovenous malformation management: case series. J Neurosurg 118(5):969–977 Nerva JD, Mantovani A, Barber J, Kim LJ, Rockhill JK, Hallam DK, Ghodke BV, Sekhar LN (2015) Treatment outcomes of unruptured arteriovenous malformations with a subgroup analysis of ARUBA (a randomized trial of unruptured brain arteriovenous malformations)-eligible patients. Neurosurgery 76(5):563–570 Parkinson D, Bachers G (1980) Arteriovenous malformations. Summary of 100 consecutive supratentorial cases. J Neurosurg 53(3):285–299 Saatci I, Geyik S, Yavuz K, Cekirge HS (2011) Endovascular treatment of brain arteriovenous malformations with prolonged
intranidal onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg 115(1):78–88 14. Spetzler RF, Ponce FA (2011) A 3-tier classification of cerebral arteriovenous malformations. J Neurosurg 114:842–849 15. Steiger HJ, Brückmann H, Mayer T, Schmid-Elsaesser R, Zausinger S (2004) Congested residual nidus after preoperative intranidal embolization in midsize cerebral arteriovenous malformations of 3–6 cm in diameter. Acta Neurochir (Wien) 146(7):649–657 16. Strauss I, Frolov V, Buchbut D, Gonen L, Maimon S (2013) Critical appraisal of endovascular treatment of brain arteriovenous malformation using onyx in a series of 92 consecutive patients. Acta Neurochir (Wien) 155(4):611–617 17. Sun Y, Lv X, Li Y, Li A (2012) Complications caused by cerebral arteriovenous malformation embolization. Neuroradiol J 25(5): 541–547 18. Taylor CL, Dutton K, Rappard G, Pride GL, Replogle R, Purdy PD, White J, Giller C, Kopitnik TA Jr, Samson DS (2004) Complications of preoperative embolization of cerebral arteriovenous malformations. J Neurosurg 100(5):810–812 19. van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JW, Vandertop WP, Algra A, Klijn CJ (2011) Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 306(18):2011–2019
LETTER TO THE EDITOR - EDITORIAL
Treatment of unruptured brain AVM in the aftermath of ARUBA and the Scottish Audit of Intracranial Vascular Malformations Hans-Jakob Steiger 1,3 & Karl Schaller 2
Received: 5 June 2015 / Accepted: 8 June 2015 # Springer-Verlag Wien 2015
We appreciate the thoughtful comments of T.R. Meling and the support of a constructive strategy regarding unruptured brain AVM. The results of the ARUBA trial have been widely commented on and the weaknesses of the study have been pointed out, i.e., the lack of differentiation between Spetzler–Martin grades and treatment modalities, and the fact that the effect of microsurgical removal was not assessed by the study design [4, 8, 9]. The report of the Scottish Audit of Intracranial Vascular Malformations drew less attention, but provided essentially the same result that intervention led to a worse outcome compared to the natural history [1]. The results of ARUBA and the Scottish Audit of Intracranial Vascular Malformations showed an almost identical pattern of strokes following intervention, with initially a higher rate of events than in untreated patients and secondary regression to the rate of the natural history. Therefore, we have to accept that the way we have been treating unruptured AVM was not right and needs correction. As pointed out by Meling, the treatment-associated morbidity rates as given in the ARUBA trial, and also the Scottish Audit, are very different from the rates given in microsurgical series. The high morbidity rates of ARUBA and the Scottish Audit are the footprint of destabilized and incompletely eliminated AVM, i.e., the pattern of endovascular embolization
* Hans-Jakob Steiger [email protected] 1
Department of Neurosurgery, Heinrich-Heine-Universität, Düsseldorf, Germany
2
Department of Neurosurgery, Hôpital Universitaire de Genève, Geneva, Switzerland
3
Neurochirurgische Klinik, Universitätsklinikum, Moorenstr 5, Geb. 10.54, 40225 Düsseldorf, Germany
[19]. Without any doubt, radiosurgery contributed to the continuing stroke rate in the interventional cohorts but was unlikely a major factor for the increased rate following intervention. Despite the obvious pattern of the delayed hemorrhages in the ARUBA and the Scottish Audit cohorts, questions remain. All non-randomized series provided rates of stroke after microsurgery, radiosurgery, and embolization far below the 9– 10 % per year rate of ARUBA and the Scottish Audit. Probability of hemorrhage after successful microsurgery appears, however, to be approximately one-tenth the rate after endovascular embolization, according to the meta-analysis of van Beijnum [19]. Although the numbers of hemorrhages given in nonrandomized series remain far below the incidence rates in ARUBA and the Scottish cohort, it appears likely that endovascular therapy was the primary factor for the exorbitant event rate following intervention. Analyzing all published series, van Beijnum and coworkers found reported annual hemorrhage rates of 0.18 % after microsurgery 1.7 % after stereotactic radiosurgery and 1.7 % after embolization. The obvious destabilizing effect resulting from treatment as seen in the ARUBA and Scottish Audit cohorts is hardly explainable by radiosurgery. Endovascular intranidal embolization emerged in the 1980s as a minimally invasive alternative to surgical elimination. It was soon realized, however, that complete elimination could not be routinely achieved. The introduction of Onyx, offering more controllable intranidal dispersion, did not change the picture fundamentally, achieving complete elimination in maximally 50 % [5, 13, 16]. Embolization also remained associated with substantial complications despite technical advances. The rate of resulting morbidity or death is given in most recent series in the range of 10 % [6, 13, 18]. Furthermore, the risk of incompletely embolized AVM remains unclear on the basis of monocentric series. Lasjaunias
Acta Neurochir
and collaborators suggested that partial occlusion still reduced the risk of hemorrhage [7]. This concept justified to continue relatively uncritically with embolization as a stand-alone therapy for ruptured and unruptured AVM. During recent years, however, there has been a silent retreat of endovascular therapy as a stand-alone management of brain AVM. While in 2014 almost 40 publications on stereotactic radiosurgery for AVM are listed in PubMed, some 20 on microsurgical resection, less than ten publications focus on endovascular treatment. In comparison, PubMed listed more than 20 publications on endovascular treatment in 2005, while reports on microsurgical resection were similar to 2014 and papers on stereotactic radiosurgery were less than 20. What remains is the supportive function of endovascular therapy prior to surgery. There is no doubt that endovascular therapy was a major technical advance in the treatment of high-grade AVM. The surgical case fatality rate for brain AVM was in the range of 15 % prior to introduction of endovascular therapy and has decreased to almost zero since [12, 19]. Complex Spetzler–Martin grade 3 and 4 AVMs (corresponding to the recently introduced Spetzler-Ponce classes B and C) have become manageable with the introduction of endovascular therapy as a preparatory adjunct for subsequent microsurgical removal [14]. Regarding presurgical embolization, surgeons have become more cautious. Endovascular embolization is not innocent. Published combined procedural morbidity and mortality rates are reported around 10 % also in the more recent series [2, 6, 13, 17, 18]. It is unclear whether the risk of subsequent surgical resection decreases correspondingly. Many of us have adopted a policy of routine embolization as the first step and reserving additional microsurgery or stereotactic radiosurgery in case of incomplete endovascular obliteration. Neurosurgeons were usually very willing to accept routine preoperative embolization due to its promise to render microsurgery easier and safer, but even this concept needs to be critically re-evaluated based on current evidence. Prior work by the group of one of us described surgical problems following arterial embolization with resulting congestion of the nidus [15], and Morgan and coworkers recently found no positive effect of preoperative embolization on surgical outcome [10]. Based on current evidence, endovascular embolization can therefore not be recommended as a preoperative adjunct for Spetzler–Martin grade 1 and 2 AVMs (corresponding to Spetzler-Ponce class A). Delayed obliteration of AVM following stereotactic radiosurgery contributed to the continuing stroke rate after intervention in the ARUBA trial and the Scottish Audit. Annual hemorrhage rates after radiosurgery have been reported on the average as 1.7 % [19], therefore not significantly accounting for the 9–10 % per year stroke rate during the first 4 years in the Scottish Audit and ARUBA. Nonetheless, the position of stereotactic radiosurgery remains open at the present time. ARUBA was not designed to grasp a potential benefit of this
mode of treatment because of the inherent latency of several years. A protective effect becoming visible only after several years must not necessarily be considered negative, as long as the complication rates remain low. Studies with a follow-up of 5–20 years will be required in order to judge the position of radiosurgery conclusively. The recent work of Bervini and colleagues, Nerva and colleagues, as well as the report in the current issue provide sufficient substance to recommend microsurgery to patients with unruptured AVM Spetzler–Martin grade 1 and 2 (corresponding to Spetzler-Ponce class A) [3, 11, 14, 16]. In contrast, treatment of unruptured Spetzler–Martin grade 3 and 4 AVMs needs to be seen critically. Here, any treatment appears to be as risky as or riskier than the natural history. It is important to consider microsurgical treatment of unruptured AVMs Spetzler–Martin grade 1 and 2 as a stand-alone therapy, as it has been recently proposed by Spetzler and his group and by other eminent neurovascular surgeons [10, 14]. Unruptured brain AVM present a substantial burden for patients with a 2.3 % annual risk of rupture resulting with 50 % chance in death or permanent disability. It is necessary, however, to continue microsurgical treatment within a controlled frame, at least with accurate book keeping, in order to obtain firm data regarding risks and benefits. Hans-Jakob Steiger, Düsseldorf Karl Schaller, Geneva
References 1.
Al-Shahi Salman R, White PM, Counsell CE, du Plessis J, van Beijnum J, Josephson CB, Wilkinson T, Wedderburn CJ, Chandy Z, St George EJ, Sellar RJ, Warlow CP, Scottish Audit of Intracranial Vascular Malformations Collaborators (2014) Outcome after conservative management or intervention for unruptured brain arteriovenous malformations. JAMA 311(16):1661–1669 2. Baharvahdat H, Blanc R, Termechi R, Pistocchi S, Bartolini B, Redjem H, Piotin M (2014) Hemorrhagic complications after endovascular treatment of cerebral arteriovenous malformations. AJNR Am J Neuroradiol 35(5):978–983 3. Bervini D, Morgan MK, Ritson EA, Heller G (2011) Surgery for unruptured arteriovenous malformations of the brain is better than conservative management for selected cases: a prospective cohort study. J Neurosurg 121(4):878–990 4. Elhammady MS, Heros RC, Editorial (2014) Management of incidental cerebral AVMs in the post-ARUBA era. J Neurosurg 121(5): 1011–1014 5. Jordan JA, Llibre JC, Vazquez F, Rodríguez RM (2014) Predictors of total obliteration in endovascular treatment of cerebral arteriovenous malformations. Neuroradiol J 27(1):108–114 6. Kim LJ, Albuquerque FC, Spetzler RF, McDougall CG (2006) Postembolization neurological deficits in cerebral arteriovenous malformations: stratification by arteriovenous malformation grade. Neurosurgery 59(1):53–9, discussion 53–59 7. Meisel HJ, Mansmann U, Alvarez H, Rodesch G, Brock M, Lasjaunias P (2002) Effect of partial targeted N-butyl-cyano-acrylate embolization in brain AVM. Acta Neurochir (Wien) 144(9): 879–887
Acta Neurochir 8.
9.
10.
11.
12.
13.
Meling TR, Proust F, Gruber A, Niemela M, Regli L, Roche PH, Vajkoczy P (2014) On apples, oranges, and ARUBA. Acta Neurochir (Wien) 156(9):1775–1779 Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, Al-Shahi Salman R, Vicaut E, Young WL, Houdart E, Cordonnier C, Stefani MA, Hartmann A, von Kummer R, Biondi A, Berkefeld J, Klijn CJ, Harkness K, Libman R, Barreau X, Moskowitz AJ, International ARUBA investigators (2014) Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 383(9917):614–621 Morgan MK, Davidson AS, Koustais S, Simons M, Ritson EA (2013) The failure of preoperative ethylene-vinyl alcohol copolymer embolization to improve outcomes in arteriovenous malformation management: case series. J Neurosurg 118(5):969–977 Nerva JD, Mantovani A, Barber J, Kim LJ, Rockhill JK, Hallam DK, Ghodke BV, Sekhar LN (2015) Treatment outcomes of unruptured arteriovenous malformations with a subgroup analysis of ARUBA (a randomized trial of unruptured brain arteriovenous malformations)-eligible patients. Neurosurgery 76(5):563–570 Parkinson D, Bachers G (1980) Arteriovenous malformations. Summary of 100 consecutive supratentorial cases. J Neurosurg 53(3):285–299 Saatci I, Geyik S, Yavuz K, Cekirge HS (2011) Endovascular treatment of brain arteriovenous malformations with prolonged
intranidal onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg 115(1):78–88 14. Spetzler RF, Ponce FA (2011) A 3-tier classification of cerebral arteriovenous malformations. J Neurosurg 114:842–849 15. Steiger HJ, Brückmann H, Mayer T, Schmid-Elsaesser R, Zausinger S (2004) Congested residual nidus after preoperative intranidal embolization in midsize cerebral arteriovenous malformations of 3–6 cm in diameter. Acta Neurochir (Wien) 146(7):649–657 16. Strauss I, Frolov V, Buchbut D, Gonen L, Maimon S (2013) Critical appraisal of endovascular treatment of brain arteriovenous malformation using onyx in a series of 92 consecutive patients. Acta Neurochir (Wien) 155(4):611–617 17. Sun Y, Lv X, Li Y, Li A (2012) Complications caused by cerebral arteriovenous malformation embolization. Neuroradiol J 25(5): 541–547 18. Taylor CL, Dutton K, Rappard G, Pride GL, Replogle R, Purdy PD, White J, Giller C, Kopitnik TA Jr, Samson DS (2004) Complications of preoperative embolization of cerebral arteriovenous malformations. J Neurosurg 100(5):810–812 19. van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JW, Vandertop WP, Algra A, Klijn CJ (2011) Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 306(18):2011–2019
