Onyx use in embolization of CNS
vascular lesions in pediatric
Mohamed Nabil Hanafy
Assistant lecturer – Department of Neurosurgery
Menoufia university - Egypt
• Intracranial AVMs comprise 3 to 20 % of all
• Spinal AVMs can present anytime during
childhood. They often manifest as congestive
or compressive myelopathy, back pain and less
acutely as murmurs or pulsating para-spinal
30-50% of pediatric spontaneous ICH
Morbidity rate: 50%
Mortality rate: 5-10%
for each hemorrhagic event
Treatment is multidisciplinary
Early treatment is recommended
• Bristol and colleagues described the surgical treatment of 84
AVMs in 82 children, in this study >50% of patients received
adjuvant therapy in the form of endovascular embolization or
radiosurgery. The authors recommended the use of
embolization as a preoperative therapy for grade II to IV lesions
before surgery.
• Embolization of AVMs is
typically used to reduce nidal
size prior to resection or
radiosurgery. Improvements in
catheters and techniques have
made the "embolization for
cure" an achievable target. In
adult AVMs, the rate of
obliteration is about 10% ,
although an exceptional 40%
angiographic cure rate was
reported by Valavanis and
Onyx Liquid Embolic Agent
• Onyx (ev3 Neurovascular, Irvine, CA) was first described by
Taki et al. and Terada et al. in the 1990s. From the chemical
standpoint, it is an ethylene-vinyl alcohol copolymer
(EVOH) dissolved in dimethyl sulfoxide (DMSO).
• It is a non-adhesive and radiolucent compound. Onyxbased closure of the lumen of the targeted vessel is
obtained by means of precipitation, initiated after diffusion
of DMSO in the presence of water.
• These properties facilitate angiographic monitoring of
embolization at any stage. Fluoroscopic visualization of the
injected Onyx mass is possible through the addition of
tantalum filings.
• Onyx is supplied in ready-to-use vials.
Each vial contains ethylene-vinyl alcohol
copolymer, dimethyl sulfoxide (DMSO),
and tantalum. Ethylene-vinyl alcohol
copolymer is formed of 48 mol/L
ethylene and 52 mol/L vinyl alcohol. The
polymer is dissolved in DMSO and is
prepared in 3 different concentrations:
6.0%, 6.5%, and 8.0%. Micronized
tantalum powder(35% wt/vol) is added
for radiopacity.
• The vials are kept on a shaker(VortexGenie, Scientific Industries, Bohemia,
NY) for at least 20 minutes to ensure
proper mixing of the tantalum powder.
The lower the concentration of the
copolymer, the less viscous the agent
and the more distal penetration can be
• The use of n-BCA in brain AVMs requires experience and
skills, because intranidal flow and polymerization of nBCA are quick and largely unpredictable.
• The use of Onyx reversed the traditional “inject and run”
approach adopted with acrylic glue is replaced by the need
and possibility for slow progressive injection lasting several
• Onyx 18 and Onyx 34 have been approved by the Food and
Drug Administration (FDA)in July 2005 for the pre-surgical
embolization of brain AVMs in adults. The use of Onyx in
pediatric patients is still off-label.
• The safety and efficacy of the use of Onyx in embolization of
CNS arteriovenous lesions in pediatric patients aren't well
Review of the available reports
• Germanwala et al. reported on a 1 year old child with a
residual vein of Galen malformation who had been treated
with coils via trans-arterial and trans-venous routes at the age
of 20 days, subsequently embolized to closure by using Onyx
* Germanwala AV, Vora NA, Thomas AJ, Jovin T, Gologorsky Y, Horowitz MB: Ethylenevinylalcohol
copolymer (Onyx-18) used in endovascular treatment of vein of Galen malformation. Childs
Nerv Syst 24:135–138, 2008
• Eddleman et al. described 2 cases of infectious intracranial
aneurysms, one of them was treated totally and uneventfully
with Onyx 18, and the other one was partly obliterated with
coils then Onyx 18 was used for complete obliteration. In the
second case distal Onyx migration happened but didn't result
in any neurologic deficits.
Eddleman CS, Surdell D, DiPatri A Jr, Tomita T, Shaibani A: Infectious intracranial aneurysms in
the pediatric population: endovascular treatment with Onyx. Childs Nerv Syst 24: 909–915,
Jankowitz et al. reported on 21 procedures done on 6 patients to treat 8 lesions. 4
patients had brain AVMs (one of the patients had 3 AVMs) and 2 patients had VOGMs.
Onyx was used alone to obliterate 3 lesions, while coils and embospheres were used
before Onyx in the rest of cases.
The procedures were complicated by transient neurological changes in 1 patient with
brain AVM and death in the 2 patients with VOGMs within 24 hours of embolization
due to intracranial hemorrhage.
• Thiex et al. presented the first large series of Onyx
embolization in CNS AV lesions in children.
• The report included 15 pediatric patients who underwent
36 transarterial embolizations by using Onyx for CNS AV
• Underlying pathologies included brain AV malformations(AVMs) (n
= 7), vein of Galen malformations (n = 4), dural AV fistulas (n = 2),
and spinal AVMs (n = 2). For 7 procedures in very high-flow lesions,
detachable coils were deployed before Onyx embolization, whereas
in 29 procedures, Onyx was the sole embolic agent.
• Embolization was complete in 2 patients, nearly complete in 9
patients, and partial in 4 patients. Following staged embolization, 7
patients underwent surgical resection without significant blood loss
and with good functional outcome in all cases.
• Clinically silent non-target embolization was encountered in 2 of 36
procedures. After 3 of the 36 embolizations, patients developed
transient neurologic symptoms, all of which resolved to baseline
within 24 hours.
• The study reported no vessel perforation, vessel dissection,
unintended vessel occlusion, or stuck catheters. There were no
post-embolization hemorrhages or territorial infarcts. There was
neither permanent neurologic morbidity nor mortality.
• Regarding the techniques of embolization, Thiex et al. preferred staged
embolization and described the "stacking technique" where Onyx 34 was
first slowly injected by using rapid gentle taps under fluoroscopic
guidance, with pauses of 15 seconds to 2 minutes to create a plug around
the microcatheter tip, providing the equivalent of a wedged microcatheter
position. Care was taken not to allow significant reflux of Onyx up the
microcatheter tip (<10 mm in a straight vessel, and <5 mm in a tortuous
vessel of small caliber). In most not purely fistulous cases, the Onyx 34
syringe was then exchanged for the Onyx 18, to allow better penetration
of nidal vessels. In purely fistulous cases, Onyx34 was used throughout.
• In 7 cases of high-flow AV fistulas or purely fistulous component of a
mixed lesion, platinum coils (Guglielmi detachable coil, BostonScientific;
or Axium; ev3) were deployed as close to the point of AV shunt as
possible, to reduce rapid inflow into the vein. After coil deployment, Onyx
could be injected with excellent flow control, permeating through the coil
mass to the shunt point.
• Regarding follow up rules, an immediate postoperative angiogram was
obtained when embolization was followed by surgical resection. Follow-up
angiography was scheduled 6 months following definitive treatment.
• Soltanolkotabi et al. managed to puplish a larger series of Onyx
embolization in CNS AV lesions in pediatric patients. Twenty-five patients
(mean age 10.5 years) underwent a total of 38 procedures. An aggregate
of 56pedicles were embolized (mean 1.47 per session).Complete
obliteration of the AVM in 3 cases (12%) and partial obliteration in 22
cases (88%). A total of 23 patients underwent surgical treatment. The
mean preoperative AVM devascularization in these cases was 72%. One
patient was treated with radiosurgery following Onyx embolization.
Overall, 10 complications occurred in a total of 38 procedures (26.3%).
None of the complications resulted in permanent neurological morbidity.
• The rate of transient neurological complications was
10.5% (4 of 38 procedures) and the rate of transient
non-neurological complications was 5.3% (2 of 38
procedures). The remaining 4 complications were
clinically silent (rate of 10.5%).
• There were no procedure-related deaths in this study
• There was no significant difference in patients with
and without complications in terms of demographic
characteristics, AVM grade, or embolization features
(p ≥ 0.2).Deep venous drainage was associated with
higher complication rates (p = 0.03).
• Ashour et al. described 105 endovascular procedures on 69 patients
with heterogeneous group of vascular disorders and tumors. The
group included 52 patients(75%) with primary vascular lesions:
• 34 cerebral AVMs
• 6 VOGMs
• 4 DAVFs
• 3 Spinal AVFs
• 3 Head and neck AVMs
• 2 Mycotic cerebral aneurysms
17 patients (25%) with hypervascular tumors:
• 9 juvenile nasal angiofibromas (JNAs)
• 3 spinal aneurysmal bone cysts
• 1 cerebellar MB
• 1 cerebellar hemangioblastoma
• 1 supratentorial GBM
• 1 scalp hemangioma
• 1 sacral giant cell tumor
• The mean number of procedures per patient was 1.52 (range, 1-6). Mean
number of pedicles embolized per procedure was 1.7 (range, 0-6).Coils
were used adjunctively in 20 (19%), n-BCA in 17 (16%), and polyvinyl
alcohol particles in 2 (2%) procedures.
• The author described complications in 25 of 105 total procedures (23.8%),
of which 9 (8.6%)were clinically silent, 14 (13.3%)produced transient
deficits, and 2 (1.9%) produced permanent deficits.
• No significant differences found between those who did and those who
did not experience complications in terms of age, sex, mean pedicles
embolized, mean estimated AVM devascularization, Spetzler-Martin AVM
grade, AVM pretreatment Rankin Scale score, use of coils/n-BCA, or
institution at which the embolization was performed. No procedurerelated deaths were reported; however, 2 deaths occurred remotely after
and were unrelated to embolization.
• Fifty-one embolization procedures were done for 34 cerebral AVMs, of
which 4 cases (11.7%) were totally obliterated by embolization alone, and
24 cases (71%) underwent post-procedural complete surgical excision. Of
the remaining 6 AVMs, 1 was partially embolized and subsequently
treated with Gamma Knife radiosurgery, and 5 were partially obliterated
after embolization and either are being followed up or further treatments
are planned.
Fifteen procedures (29.4%) had complications in the form of:
• 3 non-target cerebral artery-to-artery embolizations
• 2 microcatheter-related vessel perforations
• 2 intracerebral hemorrhages
• 2 episodes of focal cerebral edema
• 2 episodes of DMSO-induced pulmonary edema
• 1 embolization territory infarct
• 1 nontarget cerebral-to-pulmonary-artery embolization
• 1 retained microcatheter
• 1 episode of contrast-induced bronchospasm.
• Five complications (9.8%) were clinically silent, 9 (17.6%)produced
transient deficits, and 1 (2.0%) produced a permanent deficit.
• Six VOGMs underwent 15 embolization procedures. Four
cases are being followed up clinically with known residual
lesions. One case had total obliteration and another case had
near total obliteration. Complications happened in 6 of 15
procedures (40%) in the form of 3 small embolization territory
infarcts, 1 IVH requiring temporary ventriculostomy, 1 nontarget cerebral-to-pulmonary-artery embolization, and 1
retained microcatheter, and none had permanent deficits.
• Three out of 4 DAVF cases had total obliteration using both
transarterial and transvenous routes. Two mycotic cerebral
aneurysms were completely occluded with Onyx, but one of
them had permanent neurological morbidity resulting from
postembolization ischemia in the territory of the arterial
branch from which the mycotic aneurysm arose.
The extracranial vascular lesions included uneventful embolization for 2 patients
with masticator space AVMs and 1 patient with a forehead AVM. Three patients
had spinal AVFs; there was1 case of epidural AVF and 1 case of type IV
perimedullary AVF, 2both completely obliterated with Onyx. The third patient had
2 type IV perimedullary AVFs: 1 completely obliterated by Onyx embolization alone
and 1 surgically resected without endovascular treatment.
• Eighteen tumor embolizations were carried out in 17
patients with an 85% mean post-procedural
• Four JNA cases were embolized directly via an
endoscopic endonasal puncture ; the remaining14
embolizations (78%) were performed via a standard
trans-femoral approach.
• Complications occurred in 2 of 18 tumor embolization
procedures (11.1%): 1 transient episode of facial
ischemia after JNA embolization and 1 clinically silent
cerebellar MB embolization. There were no permanent
• The complication rate approximating 1 in 4 cases is
somewhat alarming, although few long-term deficits were
appreciated. This may serve as commentary on the
plasticity of the pediatric brain rather than the severity of
the complications.
• Despite the big number of patients in this study, the study
has some limitations:
 Diverse pathological entities studied
 Different approaches (in some tumors endoscopic direct puncture
and injection was used)
 Potential differences in treatment style between the 2 participating
 Retrospective nature
 Lack of control groups
 Restricted follow-up
• Squid (Emboflu, Switzerland) is a new EVOH copolymer that has been
introduced to clinical practice recently with 4 different formulations (18, 18LD,
12 and 12LD.)The LD versions have 30% less tantalum which may help visualize
structures behind dense embolic casts under X ray. The micronized tantalum
particles in Squid are smaller than Onyx and allegedly provide a more
homogeneous solution. Squid offers less viscous formulation (Squid 12)for
improved vascular penetration and as a lower density formulation (Squid LD)
compared to Onyx.
• Akmangit et al. reported on 28 patients (16 AVMs, 9 AV fistulas, 2 tumors and 1
AICA aneurysm) who were treated with Squid 18 and Squid 12.
Complication avoidance
• Microcatheter-Related Vessel Perforation
• DMSO-compatible catheters required for Onyx embolization
are stiffer and less flexible at the tip and require a microwire
for navigation
• The tortuous anatomy and small dysplastic feeding vessels in
pediatric patients
 Choose safer pedicles
 Avoid forceful injection of Onyx or contrast
• Microcatheter entrapment
• The FDA declared that neither Onyx nor the catheter is intended be
a long-term implant, and patients may need additional medical
interventions to have the catheter removed if it becomes
• Since Jan. 1, 2005, the FDA has received more than 100 reported
cases, including nine patient deaths, of catheter breakage that may
be related to catheter entrapment.
• In some cases the catheter could be removed. In at least 54 of
these cases, it was not possible to remove the catheter.
• In April 2012, the FDA approved changes to the physician and
patient labeling that reflect the risks related to catheter
 Leaving the catheter is safer than forceful extraction trials
 Maintain anticoagulation therapy
• Non-target Embolization
• cerebral artery-to-artery / cerebral artery–to–pulmonary
• Injected Onyx within the catheterized vessel exits the
microcatheter tip in the shape of a “string” rather than a
“ball,” making visualization of the Onyx difficult despite
roadmap imaging, allowing unrecognized transit through
the venous system into the pulmonary artery.
 avoid early occlusion of the venous drainage
 Control the depth and speed of penetration by using the
stacking technique or the plug and push technique, or
you can use coils before onyx to slow the flow
• Hemorrhagic Complications
• FDA Onyx/n-BCA equivalence trial, 1 hemorrhage (rate of 2%)
and 1 stroke (rate of 2%), both causing permanent deficits,
were reported in 54 adult AVM patients that underwent
preoperative Onyx embolization.
 Staged embolization is preferred by most of the authors
specially when hemodynamic instability is expected
 Be cautious in the final stages of complete embolization when
the risk of compromising the venous outflow is greatest.
• DMSO-related toxicity
• The reported average dose during FDA trials leading to
approval of Onyx for cerebral AVMs was 205 mg/kg
• DMSO toxicity is more common in children compared with
 Avoid fast injections
 Be cautious in the presence of arteriovenous shunting
 Staged embolization for large lesions
• Radiation exposure
• total patient radiation exposure may be related in part to the
longer injection times and the ability to perform multiple
intra-procedural angiographic runs when Onyx is used.
• The topic isn’t well studied
• No specific effort to minimize radiation exposure was
mentioned in any of the studies
• The available reports on the use of Onyx in pediatric
neurointerventions assume that Onyx can be used effectively
for embolization of pediatric cranial and spinal vascular
lesions and tumors with low permanent morbidity
• Future prospective controlled trials are needed with more
specification of the pathological entities under treatment
Thank you

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