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Hemorrhagic stroke
ORIGINAL RESEARCH
Neurological outcomes and cure rates of embolization of brain arteriovenous malformations with n-butyl cyanoacrylate or Onyx: a meta-analysis Abdussalam Elsenousi, Victor A Aletich, Ali Alaraj Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, USA Correspondence to Dr A Alaraj, Department of Neurosurgery (MC-799), Neuropsychiatric Institute, University of Illinois at Chicago, 912 S Wood St, Chicago, IL 60612-7329, USA; [email protected] Received 25 August 2014 Revised 21 November 2014 Accepted 1 December 2014
ABSTRACT Background In the past decade, preoperative endovascular embolization of cerebral arteriovenous malformations (AVMs) became an essential tool in the treatment of these entities. With the current expansion of technology and wide incorporation of new devices, the indications for the use of endovascular embolization have expanded to include embolization for cure. This has been facilitated by the wide use of the new liquid embolic agents (ethylene-vinyl alcohol co-polymer (EVOH)) in addition to n-butyl cyanoacrylate (NBCA). The aim of this study was to review the current published literature for these two agents and report on permanent neurological injuries and cure rate. Methods Published literature citing embolization results for AVMs using liquid embolic agents was reviewed. Papers reporting on permanent complication rates and complete angiographic cure were reviewed. A meta-analysis was performed based on these two variables for the two embolic agents. Results 103 studies met the selection criteria. Poor neurological outcomes for NBCA and EVOH were 5.2% and 6.8%, respectively (OR 1.4; p=0.56). AVM complete obliteration rate was seen in 13.7% in the NBCA group and in 24% in the EVOH group (OR 1.9). This OR decreased to 1.35 in the subgroup analysis for patients treated after the year 2000. Conclusions NBCA continues to have a trend towards lower permanent complication rates, but EVOH had higher angiographic cure rates. The recent literature has demonstrated an increase in the cure rate of AVMs with endovascular embolization techniques yet with a possible increase in permanent neurological deficits and mortality.
INTRODUCTION
To cite: Elsenousi A, Aletich VA, Alaraj A. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2014-011427
Since the introduction of the embolization of cerebral arteriovenous malformations (AVMs) in 1960 by Luessenhop and Spence using methylmethacrylate embolospheres,1 the embolization procedure gradually became an integral part of the multimodality paradigm in the treatment of brain AVMs. The goals of embolization have evolved over the past several decades, beginning as preoperative adjuncts to facilitate AVM resection.2 Although not currently approved by the US Food and Drug Administration (FDA), embolization prior to radiosurgery is performed to reduce nidal size or eliminate high risk features.3 Recently, with the expansion of experience and advancement of endovascular techniques, much debate has ensued about the appropriate role of embolization,4 with
an emergent trend focusing on performing embolization for angiographic cure.5–7 A wide variety of embolic agents have been used to treat AVMs although as of the current time only a few agents are widely used. These agents include the liquid embolic agents n-butyl cyanoacrylate (NBCA) (TruFill; Codman and Shurtleff Inc, Raynham, Massachusetts, USA), ethylene-vinyl alcohol copolymer (EVOH) (Onyx; eV3-Covedien, Irvine, California, USA) and, to a lesser degree, embolic particles such as polyvinyl alcohol (PVA) (Contour; Boston Scientific, Natick, Massachusetts, USA).8 In the USA, both NBCA and EVOH are FDA approved as adjuncts for preoperative surgical resection.9 10 NBCA and EVOH received FDA approval in 2000 and 2005, respectively. NBCA has several advantages, including its complete occlusion of vessels, high permanence, and immediate reaction time. The major drawback of NBCA is the high amount of skill required for its proper use. Several complications can arise during use, including catheter entrapment in the occluded vessel.11 Polymerization can also spread distally or reflux proximally to the intended location if NBCA is not used properly and skillfully. The advantages of EVOH include its nonadhesive nature. This allows for longer injection times and the ability to temporarily suspend embolization and proceed with further angiography mid procedure if necessary. Although the material is not adhesive and will not adhere to the catheter, there is still a risk of embedding the catheter in EVOH as it refluxes around the catheter tip.12 In this paper, we sought to review the published literature and perform a meta-analysis of the reported permanent morbidity/mortality and cure rate using these two agents.
METHODS A systematic review search was done for all available published studies on PubMed and Ovid Medline from January 1980 to November 2013. Reference lists from the identified studies were reviewed to uncover any potential studies that may have been missed in previous searches. Keywords included in the search were ‘N-butyle-2-cyanoacrylate; NBCA; Histoacryl; TruFill; ethylene vinyl alcohol copolymer; EVOH, Onyx’, and ‘brain arteriovenous malformation’. Studies were selected based on the following criteria: (1) clinical trials where at least one of the agents was included in prospective studies, retrospective studies, or an independent arm; (2) NBCA
Elsenousi A, et al. J NeuroIntervent Surg 2014;0:1–8. doi:10.1136/neurintsurg-2014-011427
1
Downloaded from http://jnis.bmj.com/ on March 14, 2015 - Published by group.bmj.com
Hemorrhagic stroke Table 1
Characteristics of n-butyl cyanoacrylate studies
Studies
No of patients
Males (n (%))
Study period
Grades I, II (%)
Agent
Wilams et al22 Jafar et al23 Wikholm24* DeMeritt et al25 Dubrun et al26 Deruty et al27 Liu et al28 Hartmann et al29 n-BCA trial30 FDA trial31 Yu et al32 Klurfan et al33 Pongpech et al34† Bhattacharya et al35 Li et al36 Raymond et al37 Ledezm et al38 Cronqvist et al39‡ Velat et al40 Loh et al41 Sahlein et al42§
8 20 134 30 54 52 103 233 52 54 27 155 176 127 469 227 168 21 60 63 130
5 (62.5) 9 (45) NA NA NA NA NA 109 (46.8) 33 (63.5) 27 (50) 15 (55.6) 110 (71) NA NA 296 (63.1) 103 (45.4) 103 (61.3) 15 (71.4) 35 (58.3) 31 (49.2) 64 (49.2)
NA 1989–1990 1987–1992 1992–1993 1994–1995 1989–1995 1987–1998 1991–1998 1996–1999 NA 1995–1997 1994–2004 1995–2005 1998–2005 1988–2005 1994–2004 1993–2004 1999–2003 2002–2006 2001–2003 1997–2006
NA NA NA 10 NA 55 24 24 34 51 51 NA 38 NA 56 NA 38 38 88 50 33
NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA
(all), PVA (1)
(all), coil (2)
(all), EVOH (5 embolized)
(all), PVA (15%)
*One case embolized with PVA. †Coil was used in two cases. ‡EVOH was used in five sessions. §PVA was used as complementary in 15% of patients. EVOH, ethylene-vinyl alcohol co-polymer; NA, not available; NBCA, n-butyl cyanoacrylate; PVA, polyvinyl alcohol.
Table 2
Characteristics of ethylene-vinyl alcohol co-polymer studies
Study
No of patients
Jahan et al43 FDA trial31 Joseph et al44 Leonardi et al45* Tevah et al.46† Pierot et al47 Perez-Higueras et al7 Weber et al48 van Rooij et al13‡ Katsaridis et al49§
23 46 5 34 24 48 45 47 44 101
Velat et al40 Panagiotopoulos 6 Geo et al50 Pan et al51 Loh et al41 Maimon et al52 ¶** Abud et al53 Xu et al54 Saatci et al55†† van Rooij et al14 Jadadeesan et al56
20 82 115 20 54 43 17 86 350 24 4
Males (n (%))
Study period
Grades I, II (%)
Agent
8 (34.8) 20 (43.5) 2 (40) 17 (50) 11 (45.8) 23 (47.9) 22 (48.9) 31 (66) 26 (59.1) 58 (57.4)
1998–1999 NA 2004–2005 NA 2004–2005 2003–2005 1999–2004 2002–2004 2000–2005 2004–2007
30.4 54.3 NA 0.0 NA NA NA 53.2 NA 24.8
10 (50) 41 (50) 72 (62.6) 14 (70) 24 (44.4) 27 (62.8) 8 (47.1) 51 (59.3) 206 (58.9) 17 (70.8) 1 (25)
2002–2006 2002–2008 2003–2007 2006–2008 2001–2003 2006–2007 2008–2009 2004–2007 1999–2008 2008–2011 2002–2004
75.0 72.0 33.0 45.0 53.7 18.6 47.1 18.6 45.1 83.3 25.0
EVOH EVOH EVOH EVOH (all), (NBCA, coil in 1 patient) EVOH (all), (NBCA in 2 patients) EVOH EVOH EVOH EVOH (all), (NBCA in 2 patients) EVOH (all), PVA (15.1%), NBCA (7.8%), coil (0.9%) EVOH EVOH EVOH EVOH EVOH EVOH (all), NBCA in 3 patients EVOH EVOH EVOH (all), NBCA (12%) EVOH EVOH
In addition to EVOH, the following agents were used as a complementary agent(s): *NBCA and coil were used in one case. †NBCA was used in 2 cases. ‡NBCA was used in 2 cases. §Particle in 15.1%, NBCA in 7.8%, and coil in 0.9% of patients. ¶Detachable tip (Sonic) was used. **NBCA in 3 cases. ††NBCA in 12% of patients. EVOH, ethylene-vinyl alcohol co-polymer; NA, not available; NBCA, n-butyl cyanoacrylate; PVA, polyvinyl alcohol.
2
Elsenousi A, et al. J NeuroIntervent Surg 2014;0:1–8. doi:10.1136/neurintsurg-2014-011427
Downloaded from http://jnis.bmj.com/ on March 14, 2015 - Published by group.bmj.com
Hemorrhagic stroke Table 3 Characteristics of the studies
Age (years) Gender (male) (%) Grades I–II (%) Session rate Presentation (%) Hemorrhage Seizure Headache Neurological deficit Incidental and other
NBCA (n=2363)
EVOH (n=1232)
p Value
35.8 56.6 44 1.8
35.9 56 41.5 1.6
0.8 0.2 0.9 0.5
47 28 12 6 7
41 33 12 7 7
0.3 0.2 0.9 0.4 0.8
EVOH, ethylene-vinyl alcohol co-polymer; NBCA, n-butyl cyanoacrylate.
or EVOH exclusively or predominantly used in the studies; and (3) outcomes: all mortalities and permanent morbidity events related to the embolization procedures for each agent were reported as complication events. A secondary outcome was the complete obliteration rate of AVMs with embolization alone. Exclusion criteria included: (1) studies reporting on more than one agent being used to embolize patients (except if used in small percentages as a complement to the main agent that was intended to treat the patient); (2) studies conducted on very small AVMs (
Hemorrhagic stroke
ORIGINAL RESEARCH
Neurological outcomes and cure rates of embolization of brain arteriovenous malformations with n-butyl cyanoacrylate or Onyx: a meta-analysis Abdussalam Elsenousi, Victor A Aletich, Ali Alaraj Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, USA Correspondence to Dr A Alaraj, Department of Neurosurgery (MC-799), Neuropsychiatric Institute, University of Illinois at Chicago, 912 S Wood St, Chicago, IL 60612-7329, USA; [email protected] Received 25 August 2014 Revised 21 November 2014 Accepted 1 December 2014
ABSTRACT Background In the past decade, preoperative endovascular embolization of cerebral arteriovenous malformations (AVMs) became an essential tool in the treatment of these entities. With the current expansion of technology and wide incorporation of new devices, the indications for the use of endovascular embolization have expanded to include embolization for cure. This has been facilitated by the wide use of the new liquid embolic agents (ethylene-vinyl alcohol co-polymer (EVOH)) in addition to n-butyl cyanoacrylate (NBCA). The aim of this study was to review the current published literature for these two agents and report on permanent neurological injuries and cure rate. Methods Published literature citing embolization results for AVMs using liquid embolic agents was reviewed. Papers reporting on permanent complication rates and complete angiographic cure were reviewed. A meta-analysis was performed based on these two variables for the two embolic agents. Results 103 studies met the selection criteria. Poor neurological outcomes for NBCA and EVOH were 5.2% and 6.8%, respectively (OR 1.4; p=0.56). AVM complete obliteration rate was seen in 13.7% in the NBCA group and in 24% in the EVOH group (OR 1.9). This OR decreased to 1.35 in the subgroup analysis for patients treated after the year 2000. Conclusions NBCA continues to have a trend towards lower permanent complication rates, but EVOH had higher angiographic cure rates. The recent literature has demonstrated an increase in the cure rate of AVMs with endovascular embolization techniques yet with a possible increase in permanent neurological deficits and mortality.
INTRODUCTION
To cite: Elsenousi A, Aletich VA, Alaraj A. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2014-011427
Since the introduction of the embolization of cerebral arteriovenous malformations (AVMs) in 1960 by Luessenhop and Spence using methylmethacrylate embolospheres,1 the embolization procedure gradually became an integral part of the multimodality paradigm in the treatment of brain AVMs. The goals of embolization have evolved over the past several decades, beginning as preoperative adjuncts to facilitate AVM resection.2 Although not currently approved by the US Food and Drug Administration (FDA), embolization prior to radiosurgery is performed to reduce nidal size or eliminate high risk features.3 Recently, with the expansion of experience and advancement of endovascular techniques, much debate has ensued about the appropriate role of embolization,4 with
an emergent trend focusing on performing embolization for angiographic cure.5–7 A wide variety of embolic agents have been used to treat AVMs although as of the current time only a few agents are widely used. These agents include the liquid embolic agents n-butyl cyanoacrylate (NBCA) (TruFill; Codman and Shurtleff Inc, Raynham, Massachusetts, USA), ethylene-vinyl alcohol copolymer (EVOH) (Onyx; eV3-Covedien, Irvine, California, USA) and, to a lesser degree, embolic particles such as polyvinyl alcohol (PVA) (Contour; Boston Scientific, Natick, Massachusetts, USA).8 In the USA, both NBCA and EVOH are FDA approved as adjuncts for preoperative surgical resection.9 10 NBCA and EVOH received FDA approval in 2000 and 2005, respectively. NBCA has several advantages, including its complete occlusion of vessels, high permanence, and immediate reaction time. The major drawback of NBCA is the high amount of skill required for its proper use. Several complications can arise during use, including catheter entrapment in the occluded vessel.11 Polymerization can also spread distally or reflux proximally to the intended location if NBCA is not used properly and skillfully. The advantages of EVOH include its nonadhesive nature. This allows for longer injection times and the ability to temporarily suspend embolization and proceed with further angiography mid procedure if necessary. Although the material is not adhesive and will not adhere to the catheter, there is still a risk of embedding the catheter in EVOH as it refluxes around the catheter tip.12 In this paper, we sought to review the published literature and perform a meta-analysis of the reported permanent morbidity/mortality and cure rate using these two agents.
METHODS A systematic review search was done for all available published studies on PubMed and Ovid Medline from January 1980 to November 2013. Reference lists from the identified studies were reviewed to uncover any potential studies that may have been missed in previous searches. Keywords included in the search were ‘N-butyle-2-cyanoacrylate; NBCA; Histoacryl; TruFill; ethylene vinyl alcohol copolymer; EVOH, Onyx’, and ‘brain arteriovenous malformation’. Studies were selected based on the following criteria: (1) clinical trials where at least one of the agents was included in prospective studies, retrospective studies, or an independent arm; (2) NBCA
Elsenousi A, et al. J NeuroIntervent Surg 2014;0:1–8. doi:10.1136/neurintsurg-2014-011427
1
Downloaded from http://jnis.bmj.com/ on March 14, 2015 - Published by group.bmj.com
Hemorrhagic stroke Table 1
Characteristics of n-butyl cyanoacrylate studies
Studies
No of patients
Males (n (%))
Study period
Grades I, II (%)
Agent
Wilams et al22 Jafar et al23 Wikholm24* DeMeritt et al25 Dubrun et al26 Deruty et al27 Liu et al28 Hartmann et al29 n-BCA trial30 FDA trial31 Yu et al32 Klurfan et al33 Pongpech et al34† Bhattacharya et al35 Li et al36 Raymond et al37 Ledezm et al38 Cronqvist et al39‡ Velat et al40 Loh et al41 Sahlein et al42§
8 20 134 30 54 52 103 233 52 54 27 155 176 127 469 227 168 21 60 63 130
5 (62.5) 9 (45) NA NA NA NA NA 109 (46.8) 33 (63.5) 27 (50) 15 (55.6) 110 (71) NA NA 296 (63.1) 103 (45.4) 103 (61.3) 15 (71.4) 35 (58.3) 31 (49.2) 64 (49.2)
NA 1989–1990 1987–1992 1992–1993 1994–1995 1989–1995 1987–1998 1991–1998 1996–1999 NA 1995–1997 1994–2004 1995–2005 1998–2005 1988–2005 1994–2004 1993–2004 1999–2003 2002–2006 2001–2003 1997–2006
NA NA NA 10 NA 55 24 24 34 51 51 NA 38 NA 56 NA 38 38 88 50 33
NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA NBCA
(all), PVA (1)
(all), coil (2)
(all), EVOH (5 embolized)
(all), PVA (15%)
*One case embolized with PVA. †Coil was used in two cases. ‡EVOH was used in five sessions. §PVA was used as complementary in 15% of patients. EVOH, ethylene-vinyl alcohol co-polymer; NA, not available; NBCA, n-butyl cyanoacrylate; PVA, polyvinyl alcohol.
Table 2
Characteristics of ethylene-vinyl alcohol co-polymer studies
Study
No of patients
Jahan et al43 FDA trial31 Joseph et al44 Leonardi et al45* Tevah et al.46† Pierot et al47 Perez-Higueras et al7 Weber et al48 van Rooij et al13‡ Katsaridis et al49§
23 46 5 34 24 48 45 47 44 101
Velat et al40 Panagiotopoulos 6 Geo et al50 Pan et al51 Loh et al41 Maimon et al52 ¶** Abud et al53 Xu et al54 Saatci et al55†† van Rooij et al14 Jadadeesan et al56
20 82 115 20 54 43 17 86 350 24 4
Males (n (%))
Study period
Grades I, II (%)
Agent
8 (34.8) 20 (43.5) 2 (40) 17 (50) 11 (45.8) 23 (47.9) 22 (48.9) 31 (66) 26 (59.1) 58 (57.4)
1998–1999 NA 2004–2005 NA 2004–2005 2003–2005 1999–2004 2002–2004 2000–2005 2004–2007
30.4 54.3 NA 0.0 NA NA NA 53.2 NA 24.8
10 (50) 41 (50) 72 (62.6) 14 (70) 24 (44.4) 27 (62.8) 8 (47.1) 51 (59.3) 206 (58.9) 17 (70.8) 1 (25)
2002–2006 2002–2008 2003–2007 2006–2008 2001–2003 2006–2007 2008–2009 2004–2007 1999–2008 2008–2011 2002–2004
75.0 72.0 33.0 45.0 53.7 18.6 47.1 18.6 45.1 83.3 25.0
EVOH EVOH EVOH EVOH (all), (NBCA, coil in 1 patient) EVOH (all), (NBCA in 2 patients) EVOH EVOH EVOH EVOH (all), (NBCA in 2 patients) EVOH (all), PVA (15.1%), NBCA (7.8%), coil (0.9%) EVOH EVOH EVOH EVOH EVOH EVOH (all), NBCA in 3 patients EVOH EVOH EVOH (all), NBCA (12%) EVOH EVOH
In addition to EVOH, the following agents were used as a complementary agent(s): *NBCA and coil were used in one case. †NBCA was used in 2 cases. ‡NBCA was used in 2 cases. §Particle in 15.1%, NBCA in 7.8%, and coil in 0.9% of patients. ¶Detachable tip (Sonic) was used. **NBCA in 3 cases. ††NBCA in 12% of patients. EVOH, ethylene-vinyl alcohol co-polymer; NA, not available; NBCA, n-butyl cyanoacrylate; PVA, polyvinyl alcohol.
2
Elsenousi A, et al. J NeuroIntervent Surg 2014;0:1–8. doi:10.1136/neurintsurg-2014-011427
Downloaded from http://jnis.bmj.com/ on March 14, 2015 - Published by group.bmj.com
Hemorrhagic stroke Table 3 Characteristics of the studies
Age (years) Gender (male) (%) Grades I–II (%) Session rate Presentation (%) Hemorrhage Seizure Headache Neurological deficit Incidental and other
NBCA (n=2363)
EVOH (n=1232)
p Value
35.8 56.6 44 1.8
35.9 56 41.5 1.6
0.8 0.2 0.9 0.5
47 28 12 6 7
41 33 12 7 7
0.3 0.2 0.9 0.4 0.8
EVOH, ethylene-vinyl alcohol co-polymer; NBCA, n-butyl cyanoacrylate.
or EVOH exclusively or predominantly used in the studies; and (3) outcomes: all mortalities and permanent morbidity events related to the embolization procedures for each agent were reported as complication events. A secondary outcome was the complete obliteration rate of AVMs with embolization alone. Exclusion criteria included: (1) studies reporting on more than one agent being used to embolize patients (except if used in small percentages as a complement to the main agent that was intended to treat the patient); (2) studies conducted on very small AVMs (
