Sergio A. Vargas, Carlos Diaz, Diego A. Herrera, Arthur B. Dublin
From the Universidad de Antioquia, Department of Radiology, Medellin, Colombia (SAV, CD, DAH); University of California Davis Medical Center, Department of Diagnostic Radiology, Sacramento, CA (ABD).
OBJECTIVE: To report a single-center experience in the endovascular management of cerebral aneurysms in children with stenting and flow-diversion techniques.
METHODS: During a 7-year period, 5 male patients with six intracranial aneurysms (IA) were treated by endovascular therapy with stenting or flow-diversion. The average age was 11 years (range 6-18 years).
RESULTS: The etiology of the aneurysms was vasculopathic in 3 cases (50%), traumatic in 2 patients (33.3%), and idiopathic in 1 case (16.7%). Two-thirds of the aneurysms were giant in size. The aneurysms were most frequently located in the anterior circulation (66.7%). Fifty percent of the aneurysms were treated with stenting and coiling, and 50% were treated with flow diversion stents alone. After treatment, occlusion was graded as: partial in five aneurysms (88.3%) and complete in 1 case (16.7%). Most cases (83.3%) had a good outcome after the procedure. During follow-up, most aneurysms had progressive occlusion (80%), while the rest were unchanged (20%). Most stents and flow-diverter devices remained patent (80%). However, one Pipeline flow-diverter device in the Anterior cerebral artery (ACA) A2 segment had an asymptomatic occlusion. CONCLUSIONS: In this series, device-assisted endovascular techniques were a relatively safe and effective method of treatment of pediatric aneurysms. However, continued follow-up is required after treatment, because there are unsolved issues regarding the durability of flow-diverters and stents.
Keywords: Intracranial aneurysm, children, stent, pipeline.
Acceptance: Received July 17, 2015, and in revised form August 18, 2015. Accepted for publication September 1, 2015.
Correspondence: Address correspondence to Diego A. Herrera, Universidad de Antioquia, Department of Radiology, Medellin, Colombia. E-mail: email@example.com
J Neuroimaging 2016;26:41-45. DOI: 10.1111/jon.12305
Intracranial aneurysms (IA) in childhood account for less than 5% of aneurysms discovered in the general population. Furthermore, less than 1% of patients admitted to the emergency room with subarachnoid hemorrhage (SAH) are younger than 21 years old. There are some differences between pediatric and adult aneurysms including location, morphology, size, multiplicity, rate of spontaneous thrombosis and the susceptibility to present vasospasm.1–6 Therefore, one cannot assume that all treatment strategies used in adults are immediately applicable to a younger population.
The current treatment strategies for IAs include: expectant management, surgical clipping, and endovascular therapy.
In complex aneurysms (without a good neck, fusiform, giant or pseudoaneurysms), standard coiling or vessel sacrifice may not feasible without acceptable risk; consequently, reconstructive strategies using stents or flow-diversion devices should be considered for treatment for these types of aneurysms.
There is scarce literature reporting the use of stents and flowdiverter devices in children. In 2015, Navarro et al reported the use of flow-diverter devices for treating complex IA in three children with good results.7 However, the expected long survival after the endovascular procedure in a young population raises questions about vessel response to growth in the presence of an endoluminal device, durability of flow-diverters and stents over a long follow-up, and the safety of deploying potentially
thrombogenic material. Our goal is to expand the reported data of stenting and flow-diversion of pediatric cerebral aneurysms.
Materials and Methods
Study Design, Patients and Aneurysms
Institutional review board approval and informed written consent was obtained for this single-center retrospective case series. After reviewing our database of 23 pediatric endovascularly treated aneurysms, between January 2007 and February 2014, we found five patients with six IAs treated by stenting and flow diversion (Table 1). There were 5 male (100%) patients with an average age of 11 years (range 6-18 years). Exclusion factors included: aneurysms associated with an AVM, aneurysms related to the dural branches, incomplete clinical records or inadequate follow-up, and concomitant surgical management. Aneurysms were classified according to the pathogenetic subtype as: idiopathic, traumatic, vasculopathic, or infectious.1 Aneurysm morphology was evaluated prior to embolization, including variables such as location, size, and neck type.
Clinical Evaluation and Follow-up
Clinical evaluations were performed before and after treatment, at hospital discharge, and between 8-36 months followup period. Morbidity was defined as any worsening in modified Rankin Scale (mRS) in comparison with the initial score.
Complications were classified according to the time of the event and clinical consequences. Progressive occlusion was defined as any improvement from the initial results, as observed by follow up MRA or conventional angiography. Major recurrence was defined as the need of additional endovascular treatment. Treatment outcome was graded according to the Glasgow Out come Scale (GOS) as: (1) death (severe injury or death without recovery of consciousness); (2) persistent vegetative state (severe damage with prolonged state of unresponsiveness and a lack of higher mental functions); (3) severe disability (severe injury with permanent need for help with daily living); (4) moderate disability (no need for assistance in everyday life, employment is possible but may require special equipment); and (5) low disability (light damage with minor neurological and psychological deficits).
Endovascular Therapy Procedures
Each procedure was performed via a transfemoral under general anesthesia. All patients received an initial heparin bolus (70 UI/kg), followed by a continuous heparin infusion. Prowler- 10 (Cordis Endovascular Systems, Miami Lakes, FL), or a Prowler-select Plus (Codman, Miami Lakes, FL) or an Excelsior SL 10 (Target Therapeutics/Boston Scientific, Fremont, CA) microcatheter was navigated across the aneurysm neck. When using the stent-jail technique, two microcatheters were navigated across and inside the aneurysm. Aneurysm embolization was performed with either Guglielmi Detachable Coils (Boston Scientific/Target Therapeutics, Fremont, CA), Matrix coils (Boston Scientific/Target Therapeutics, Fremont, CA) or Hydrocoils (MicroVention, Inc, Aliso Viejo, CA). When required, a Neuroform stent (Boston Scientific/Target Therapeutics, Fremont, CA), an Enterprise stent (Cordis, Miami, FL) or the Pipeline embolization device (EV3, Irvine, CA) were deployed. At the end of the procedure, the occlusion was classified as complete, a remnant neck was present, occlusion was partial, or occlusion of the aneurysm failed. After the procedure, all patients were placed on oral aspirin (indefinitely) and clopidogrel (for 3 months).
Means and ranges were calculated for continuous variables. Descriptive statistics with number of cases and percentages were used for results presentation.
Aneurysms most commonly presented as an incidental finding (n = 4, 66.7%), followed in frequency by mass effect (n = 1, 16.7%), and with SAH (n = 1, 16.7%). The etiology of the aneurysms was vasculopathic in 3 cases (50%), traumatic in 2 patients (33.3%) and idiopathic in 1 case (16.7%) (Figures 1 and 2).
The IA mean size was 19 mm (range 4-40 mm). Most IA were large or giant (n = 4, 66.7%) versus small (n = 2, 33.3%). The aneurysms were located in the ACA in 2 cases (33.3%), in the basilar artery in 2 patients (33.3%), in the MCA in 1 case (16.7%), and in the ICA in 1 case (16.7%).
The treatment modalities were: stenting with coiling (n = 3, 50%), or deployment of flow-diverter devices (n = 3, 50%). After treatment, occlusion was graded as partial in five aneurysms (88.3%) and complete in 1 case (16.7%).
Most cases had a good outcome, with a GOS score of 5 after the procedure (n = 5, 83.3%). One patient death occurred after treatment of a giant vertebrobasilar aneurysm (stenting and embolization with hydrocoils). In this case, the patient recovered from the anesthesia without focal deficit, but after one hour presented sudden loss of consciousness, and brain death was confirmed by transcranial Doppler.
The follow-up mean period was 21.4 months (range 8-36 months). During follow-up, all patients remained stable according to mRS and GOS. Angiographically, most aneurysms had progressive occlusion (n = 4, 80%), or stay unchanged (n = 1, 20%). Most stents and flow-diverter devices remained patent(n = 4, 80%); however, one Pipeline flow-diverter device in the ACA A2 segment had an asymptomatic occlusion with distal collateral filling.
Brain aneurysms in children have different traits, when compared with adults, including: sex predilection, location, morphology, size, and multiplicity. Young children have an increased frequency of giant and fusiform aneurysms. Accordingly, one can expect that traditional coiling cannot be performed in all cases. Frequently, complex aneurysms have been treated with a deconstructive approach; however, if collateral circulation is poor, vessel sacrifice is unsafe. Thus, newer device assisted endovascular therapy techniques should be considered for the treatment of IAs in children. Unfortunately, studies focusing in the pediatric population are lacking, in part because of the low frequency of IAs in children.
In our series, most aneurysms were asymptomatic and discovered incidentally. This is different from other reports showing SAH with headache as the most frequent presenting symptom of brain aneurysms in children. The discrepancy is understandable because of the bias of including in the study only complex aneurysms treated with stenting and flow-diversion.Half of the aneurysms in our series were vasculopathic, which is higher compared to other series (10-20%). Vasculopathic aneurysms may be secondary to systemic or collagen diseases. Other entities associated with aneurysms in children are Klippel-Trenaunay, hereditary hemorrhagic telangiectasia, Moya-Moya syndrome, aortic coarctation, fibromuscular dysplasia, tuberous sclerosis, and neurofibromatosis type 1.
While the presence of a vasculopathy raises questions about a possible adverse vessel response to an endoluminal device, in the vasculopathic aneurysms we treated, after 2- and 3-year follow-up, there were no angiographic signs of intimal hyperplasia or unexpected vessel remodeling.
In a 2011 large adult series, the overall incidence of thromboembolic events was only 3.1% in unruptured aneurysms treated with the Neuroform stent-assisted technique.8 Our study did not show either early or delayed complications in the 2 patients treated with that stent. In adults, some thromboembolic complications of stent-assisted coiling have been attributed to clopidogrel resistance.9 That correlation has not been confirmed in children. Furthermore, in children, a lower clopidogrel dose per kilogram achieves comparable inhibition of platelet aggregation compared with adults, an effect in part attributed to ADP-induced hyporeactivity in the platelets of the younger population.
Table 2 summarizes the literature experience of stentassisted coiling of pediatric brain aneurysms. However, in half of these studies we could not extract specific data. Only one stent-related complication was reported in a giant basilar artery aneurysm treated with telescoping stents. This patient had stent thrombosis and posterior circulation stroke. Because there are no large series focusing exclusively on stent-assisted coiling of pediatric brain aneurysms, we can not determine whether the morbimortality is equivalent to the adult population.
In the stent-assisted treatment group, we only had one symptomatic complication resulting in a patient death (Enterprise stent-assisted coiling was performed). However, as an autopsy was not performed, we cannot completely exclude other causes of sudden death such as massive brain infarction, aneurysmal rupture, or cardiac complications.
A Pubmed search for flow-diverter treatment of brain aneurysms in children did not reveal any large study focusing exclusively on that population; nonetheless, case reports are available. The first evidence of Pipeline embolization de- vice (PED) use in pediatric patients can be inferred from the age range (11-77 years) of patients treated by Lylyk et al; however,
no specific information of treated children could be extracted from that study.19 Subsequent large studies of brain aneurysms treated with the PED showed some evidence that pediatric patients were treated with that technique, but no concrete data could be obtained for additional analysis. To date, we found four case report publications expressly describing the use of flow-diverter devices for the treatment of brain aneurysms in children. Additional information of six flow-diverted aneurysms in children could be extracted after analyzing three studies including both children and adults. This data is summarized in Table 2. If we put those previously reported eleven pediatric patients together with the three aneurysms we treated with the PED, we can presume the morbidity and mortality of the technique is low. Spontaneous PED occlusion after treatment of an ACA A2 segment aneurysm was observed; accordingly, we think the PED may not be well-suited for the treatment of small vessels or peripheral brain aneurysms in children.
Additional unsolved questions related with the use of stents and flow-diverter devices in children remain. Those issues are related to expected long survival after the endovascular procedure in a young population. The durability of flow-diverters and stents over a long follow-up is unknown, and there is the possible latent risk of deploying potentially thrombogenic material over the long term.
In this series, device-assisted endovascular techniques were a relatively safe and effective method of treatment for complex aneurysms in children. Continual and chronic follow-up is suggested after treatment, because there are unsolved issues regarding the durability of flow-diverters and stents, as well as the safety of deploying potentially thrombogenic material over the long term.
1. Aeron G, Abruzzo TA, Jones BV. Clinical and imaging features of intracranial arterial aneurysms in the pediatric population. Radiographics 2012;32:667-81.
2. Hetts SW, English JD, Dowd CF, et al. Pediatric intracranial aneurysms: new and enlarging aneurysms after index aneurysm treatment or observation. AJNR Am J Neuroradiol 2011;32:2017- 22.
3. Hetts SW, Narvid J, Sanai N, et al. Intracranial aneurysms in child- hood: 27-year single-institution experience. AJNR Am J Neuroradiol 2009;30:1315-24.
- Agid R, Jonas Kimchi T, Lee SK, et al. Diagnostic characteristics and management of intracranial aneurysms in children. Neuroimaging Clin N Am 2007;17:153-63.
- Lasjaunias P, Wuppalapati S, Alvarez H, et al. Intracranial aneurysms in children aged under 15 years: review of 59 consecu- tive children with 75 aneurysms. Childs Nerv Syst 2005;21:437-50.
- Buis DR, van Ouwerkerk WJ, Takahata H, et al. Intracranial aneurysms in children under 1 year of age: a systematic review of the literature. Childs Nerv Syst 2006;22:1395-1409.
- Navarro R, Brown BL, Beier A, et al. Flow diversion for com- plex intracranial aneurysms in young children. J Neurosurg Pediatr 2015;15:276-81.
- Lessne ML, Shah P, Alexander MJ, et al. Thromboembolic complications after Neuroform stent-assisted treatment of cerebral aneurysms: the Duke Cerebrovascular Center experience in 235 patients with 274 stents. Neurosurgery 2011;69:369-75.
- Muller-Schunk S, Linn J, Peters N, et al. Monitoring of clopidogrelrelated platelet inhibition: correlation of nonresponse with clinical outcome in supra-aortic stenting. AJNR Am J Neuroradiol 2008;29(4):786-91.
- Li JS, Yow E, Berezny KY, et al. PICOLO Investigators. Dosing of clopidogrel for platelet inhibition in infants and young children: primary results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial. Circulation 2008;117(4):553-9.
- Koroknay-Pa ́l P, Lehto H, Niemela ̈ M, et al. Long-term outcome of 114 children with cerebral aneurysms. J Neurosurg Pediatr 2012;9:636-45.
- Takemoto K, Tateshima S, Golshan A, et al. Endovascular treatment of pediatric intracranial aneurysms: a retrospective study of 35 aneurysms. J Neurointerv Surg 2014;6:432-8.
- Griauzde J, Gemmete JJ, Chaudhary N, et al. Basilar artery pseudoaneurysm presenting at 5-month follow-up after traumatic atlantooccipital dislocation in a 7-year-old girl treated with in- tracranial stent placement and coiling. BMJ Case Rep 2013;2013. pii: bcr2012010573.
- Geyik S, Yavuz K, Yurttutan N, et al. Stent-assisted coiling in endovascular treatment of 500 consecutive cerebral aneurysms with long-term follow-up. AJNR Am J Neuroradiol 2013;34:2157-62.
- Lessne ML, Shah P, Alexander MJ, et al. Thromboembolic com- plications after Neuroform stentassisted treatment of cerebral aneurysms: the Duke Cerebrovascular Center experience in 235 patients with 274 stents. Neurosurgery 2011;69:369-75.
16. Ogilvy CS, Tawk RG, Mokin M, et al. Stent-assisted coiling treatment of pediatric traumatic pseudoaneurysm resulting from tumor surgery. Pediatr Neurosurg 2011;47:442-8.
17. Biondi A, Janardhan V, Katz JM, et al. Neuroform stentassisted coil embolization of wide-neck intracranial aneurysms: strategies in stent deployment and midterm follow-up. Neurosurgery 2007;61(3):460-8.
18. Saraf R, Shrivastava M, Siddhartha W, et al. Intracranial pediatric aneurysms: endovascular treatment and its outcome. J Neurosurg Pediatr 2012;10:230-40.
19. Lylyk P, Miranda C, Ceratto R, et al. Curative endovascular re- construction of cerebral aneurysms with the pipeline embolization device: the Buenos Aires experience. Neurosurgery 2009;64:632- 42; discussion 642-3; quiz N6.
20. C ̧ inar C, Bozkaya H, Oran I. Endovascular treatment of cranial aneurysms with the pipeline flowdiverting stent: preliminary mid- term results. Diagn Interv Radiol 2013;19:154-64.
21. Piano M, Valvassori L, Quilici L, et al. Midterm and long-term follow-up of cerebral aneurysms treated with flow diverter devices: a single-center experience. J Neurosurg 2013;118:408-16.
22. Chiu AH, Cheung AK, Wenderoth JD, et al. Long-term follow- up results following elective treatment of unruptured intracranial aneurysms with the pipeline embolization device. AJNR Am J Neu- roradiol 2015. [Epub ahead of print]
23. Ikeda DS, Marlin ES, Shaw A, et al. Successful endovascular recon- struction of a recurrent giant middle cerebral artery aneurysm with multiple telescoping flow diverters in a pediatric patient. Pediatr Neurosurg 2015;50:88-93.
24. Appelboom G, Kadri K, Hassan F, et al. Infectious aneurysm of the cavernous carotid artery in a child treated with a new-generation of flow-diverting stent graft: case report. Neurosurgery 2010;66:E623- 4; discussion E624.
25. Zarzecka A, Gory B, Turjman F. Implantation of two flow diverter devices in a child with a giant, fusiform vertebral artery aneurysm: case report. Pediatr Neurol 2014;50:185-7.
26. Lubicz B, Collignon L, Raphaeli G, et al. Flow-diverter stent for the endovascular treatment of intracranial aneurysms: a prospective study in 29 patients with 34 aneurysms. Stroke 2010;41:2247-53.
27. de Barros Faria M, Castro RN, Lundquist J, et al. The role of the pipeline embolization device for the treatment of dissect- ing intracranial aneurysms. AJNR Am J Neuroradiol 2011;32: 2192-5.