i777777o66726f6e7469657273696eo6f7267z.oszar.com Open in urlscan Pro
172.67.220.76  Public Scan

Form analysis
1 forms found in the DOM

POST

<form action="" method="POST" style="all:unset;float:left;">
  <input type="hidden" name="URL_Adresi" value="https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.00179/full">
  <select name="DNS_Adresi" onchange="this.form.submit()" style="all:unset;border:1px solid silver;border-width:0;margin:0px 0px 0px 20px;background-color:transparent;color:black;line-height:20px;text-align:left;padding:0 5px;font-size:14px;">
    <option value="0" selected="true">Otomatik - 13.107.246.44</option>
    <option value="11">CloudFlare DNS</option>
    <option value="12">Türk Telekom DNS</option>
    <option value="13">Google DNS</option>
    <option value="14">Open DNS</option>
  </select>
</form>

Text Content

Skip to main content


TOP BAR NAVIGATION

Frontiers in Neurology
About us
About us
 * Who we are
 * Mission
 * Values
 * History
 * Leadership
 * Awards

 * Impact and progress
 * Frontiers' impact
 * Progress Report 2022
 * All progress reports

 * Publishing model
 * How we publish
 * Open access
 * Fee policy
 * Peer review
 * Research Topics

 * Services
 * Societies
 * National consortia
 * Institutional partnerships
 * Collaborators

 * More from Frontiers
 * Frontiers Forum
 * Press office
 * Carbon footprint
 * Career opportunities
 * Contact us

All journalsAll articles Submit your research

Search Login
Frontiers in Neurology
Sections
Sections
 * Applied Neuroimaging
 * Artificial Intelligence in Neurology
 * Autonomic Disorders
 * Cognitive and Behavioral Neurology
 * Dementia and Neurodegenerative Diseases
 * Diagnostic and Forensic Neuropathology
 * Endovascular and Interventional Neurology
 * Epilepsy
 * Experimental Therapeutics
 * Headache and Neurogenic Pain
 * Movement Disorders
 * Multiple Sclerosis and Neuroimmunology
 * Neuro-Oncology and Neurosurgical Oncology
 * Neuro-Ophthalmology
 * Neuro-Otology
 * Neurocritical and Neurohospitalist Care
 * Neuroepidemiology
 * Neurogenetics
 * Neuroinfectious Diseases
 * Neurological Biomarkers
 * Neuromuscular Disorders and Peripheral Neuropathies
 * Neurorehabilitation
 * Neurotechnology
 * Neurotrauma
 * Pediatric Neurology
 * Sleep Disorders
 * Stroke

ArticlesResearch TopicsEditorial board
About journal
About journal
 * Scope
 * Field chief editors
 * Mission & scope
 * Facts
 * Journal sections
 * Open access statement
 * Copyright statement
 * Quality

 * For authors
 * Why submit?
 * Article types
 * Author guidelines
 * Editor guidelines
 * Publishing fees
 * Submission checklist
 * Contact editorial office

About us
About us
 * Who we are
 * Mission
 * Values
 * History
 * Leadership
 * Awards

 * Impact and progress
 * Frontiers' impact
 * Progress Report 2022
 * All progress reports

 * Publishing model
 * How we publish
 * Open access
 * Fee policy
 * Peer review
 * Research Topics

 * Services
 * Societies
 * National consortia
 * Institutional partnerships
 * Collaborators

 * More from Frontiers
 * Frontiers Forum
 * Press office
 * Carbon footprint
 * Career opportunities
 * Contact us

All journalsAll articles Submit your research
Frontiers in Neurology
Sections
Sections
 * Applied Neuroimaging
 * Artificial Intelligence in Neurology
 * Autonomic Disorders
 * Cognitive and Behavioral Neurology
 * Dementia and Neurodegenerative Diseases
 * Diagnostic and Forensic Neuropathology
 * Endovascular and Interventional Neurology
 * Epilepsy
 * Experimental Therapeutics
 * Headache and Neurogenic Pain
 * Movement Disorders
 * Multiple Sclerosis and Neuroimmunology
 * Neuro-Oncology and Neurosurgical Oncology
 * Neuro-Ophthalmology
 * Neuro-Otology
 * Neurocritical and Neurohospitalist Care
 * Neuroepidemiology
 * Neurogenetics
 * Neuroinfectious Diseases
 * Neurological Biomarkers
 * Neuromuscular Disorders and Peripheral Neuropathies
 * Neurorehabilitation
 * Neurotechnology
 * Neurotrauma
 * Pediatric Neurology
 * Sleep Disorders
 * Stroke

ArticlesResearch TopicsEditorial board
About journal
About journal
 * Scope
 * Field chief editors
 * Mission & scope
 * Facts
 * Journal sections
 * Open access statement
 * Copyright statement
 * Quality

 * For authors
 * Why submit?
 * Article types
 * Author guidelines
 * Editor guidelines
 * Publishing fees
 * Submission checklist
 * Contact editorial office


Frontiers in Neurology

Sections
Sections
 * Applied Neuroimaging
 * Artificial Intelligence in Neurology
 * Autonomic Disorders
 * Cognitive and Behavioral Neurology
 * Dementia and Neurodegenerative Diseases
 * Diagnostic and Forensic Neuropathology
 * Endovascular and Interventional Neurology
 * Epilepsy
 * Experimental Therapeutics
 * Headache and Neurogenic Pain
 * Movement Disorders
 * Multiple Sclerosis and Neuroimmunology
 * Neuro-Oncology and Neurosurgical Oncology
 * Neuro-Ophthalmology
 * Neuro-Otology
 * Neurocritical and Neurohospitalist Care
 * Neuroepidemiology
 * Neurogenetics
 * Neuroinfectious Diseases
 * Neurological Biomarkers
 * Neuromuscular Disorders and Peripheral Neuropathies
 * Neurorehabilitation
 * Neurotechnology
 * Neurotrauma
 * Pediatric Neurology
 * Sleep Disorders
 * Stroke

ArticlesResearch TopicsEditorial board
About journal
About journal
 * Scope
 * Field chief editors
 * Mission & scope
 * Facts
 * Journal sections
 * Open access statement
 * Copyright statement
 * Quality

 * For authors
 * Why submit?
 * Article types
 * Author guidelines
 * Editor guidelines
 * Publishing fees
 * Submission checklist
 * Contact editorial office


Submit  your research Search Login
Download article
 * Download PDF
 * ReadCube
 * EPUB
 * XML (NLM)

SHARE ON

 * 
 * 
 * 

Export citation
 * EndNote
 * Reference Manager
 * Simple Text file
 * BibTex

2K
Total views
778
Downloads
11
Citations
Citation numbers are available from Dimensions
View article impact

View altmetric score

SHARE ON

 * 
 * 
 * 

Edited by
Diogo C. Haussen
Emory University, United States
Reviewed by
Viktor Szeder, MD, PhD, MSc, FSVIN
David Geffen School of Medicine, University of California, Los Angeles, United
States
Waldo R. Guerrero
University of South Florida, United States
Table of contents

 * Abstract
 * Introduction
 * Materials and Methods
 * Results
 * Discussion
 * Conclusions
 * Author Contributions
 * Funding
 * Conflict of Interest Statement
 * References


Export citation
 * EndNote
 * Reference Manager
 * Simple Text file
 * BibTex

Check for updates


PEOPLE ALSO LOOKED AT


ENDOVASCULAR TREATMENT OF LARGE OR GIANT NON-SACCULAR VERTEBROBASILAR ANEURYSMS:
PIPELINE EMBOLIZATION DEVICES VERSUS CONVENTIONAL STENTS

Jiejun Wang, Luqiong Jia, Zhibin Duan, Zhongxiao Wang, Xinjian Yang, Yisen Zhang
and Ming Lv


A NECROPTOSIS-RELATED LNCRNA SIGNATURE WAS IDENTIFIED TO PREDICT THE PROGNOSIS
AND IMMUNE MICROENVIRONMENT OF IDH-WILD-TYPE GBM

Chong Song, Liwen Zhu, Junwei Gu, Tong Wang, Linyong Shi, Chiyang Li, Lei Chen,
Sidi Xie and Yuntao Lu


IMAGING IDENTIFICATION AND PROGNOSIS OF THE DISTAL INTERNAL CAROTID ARTERY WITH
NEAR AND COMPLETE OCCLUSION AFTER RECANALIZATION

Tao Sun, Chao Wang, Mengtao Han, Fei Wang, Yiming He, Yunyan Wang, Xingang Li
and Donghai Wang


APPLICATION OF INTRACRANIAL PRESSURE-DIRECTED THERAPY ON DELAYED CEREBRAL
ISCHEMIA AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

Jun Yang, Junlin Lu, Runting Li, Fa Lin, Yu Chen, Heze Han, Debin Yan, Ruinan
Li, Zhipeng Li, Haibin Zhang, Kexin Yuan, Hongliang Li, Linlin Zhang, Guangzhi
Shi, Jianxin Zhou, Shuo Wang, Yuanli Zhao and Xiaolin Chen


OUTCOMES IN SYMPTOMATIC PATIENTS WITH VERTEBROBASILAR DOLICHOECTASIA FOLLOWING
ENDOVASCULAR TREATMENT

Jiejun Wang, Luqiong Jia, Xinjian Yang, Xuecang Jia, Jian Liu, Peng Liu, Zefeng
Miao, Ying Zhang, Zhongbin Tian, Kun Wang, Zhongxiao Wang, Yisen Zhang and Ming
Lv



ORIGINAL RESEARCH ARTICLE

Front. Neurol., 10 March 2019
Sec. Endovascular and Interventional Neurology
Volume 10 - 2019 | https://i646f69o6f7267z.oszar.com/10.3389/fneur.2019.00179


APPLICATION OF THE PIPELINE EMBOLIZATION DEVICE FOR GIANT VERTEBROBASILAR
DISSECTING ANEURYSMS IN PEDIATRIC PATIENTS

Updated
Jiejun Wang1†Yisen Zhang1†Ming Lv1*Xinjian Yang1*Zhongbin Tian1Jian Liu1Peng
Liu1Zefeng Miao2Luqiong Jia1Junfan Chen1Xinghuan Ding1Ying Zhang1Wei
Zhu1Wenqiang Li1Kun Wang1Zhongxiao Wang1
 * 1Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical
   University, Beijing, China
 * 2Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China

A correction has been applied to this article in:

 1. Corrigendum: Application of the Pipeline Embolization Device for Giant
    Vertebrobasilar Dissecting Aneurysms in Pediatric Patients
    
    1. Read correction

Objective: To evaluate the feasibility and effectiveness of the pipeline
embolization device (PED) for the treatment of pediatric giant vertebrobasilar
dissecting aneurysms (VBDAs).

Methods: We retrospectively reviewed our institutional clinical database and
identified 2,706 patients who presented with a diagnosis of intracranial
aneurysms from January 2016 to June 2018. Among this group, 153 patients were
diagnosed with VBDAs, and 54 of these patients underwent PED therapy. The PED
technique was used in four patients who were 18 years old or younger at the time
of presentation (two males, two females; mean age 9.25 years; age range 8–11
years).

Results: All four included pediatric patients were managed with the PED. One
patient (25%) was treated with the PED alone, while three (75%) were treated
with the PED and coils. One patient died from brainstem infarction or
compression of the brainstem, while follow-up of the other three patients
revealed favorable outcomes. The mass effect was reduced in cases 1, 2, and 3 on
follow-up MRI performed 6 months after the PED procedure.

Conclusions: PEDs could be feasible in the treatment of pediatric giant VBDAs.
However, the safety and efficacy of this method have not been clarified in this
special pediatric population, and long-term follow-up is still necessary.




INTRODUCTION

Pediatric intracranial aneurysms are exceedingly rare, accounting for <5% of all
intracranial aneurysms, and intracranial dissecting aneurysms are even rarer (1,
2). Intracranial dissection mostly involves the vertebrobasilar circulation (3).
Treatment of intracranial artery dissections is empirical, as there is an
absence of data from randomized controlled trials. Patients with intracranial
artery dissection with or without subarachnoid hemorrhage are usually treated
with surgical or endovascular procedures (4). For pediatric patients with
intracranial artery dissection, parental biases toward non-craniotomy therapy
must be thoroughly addressed before the ultimate selection of a treatment
strategy (5). Thus, endovascular procedures have become the first choice for the
treatment of pediatric intracranial dissecting aneurysms. An endovascular
procedure that has gained increasing popularity is the pipeline embolization
device (PED). However, the safety and effectiveness of the PED for pediatric
vertebrobasilar dissecting aneurysms (VBDAs) have not yet been clarified, as
most of the literature on this topic is composed of case reports. In the present
paper, we present our early experience in using the PED to treat VBDAs in four
pediatric patients. The purpose of the present study was to evaluate the
procedural feasibility and effectiveness of using the PED to treat pediatric
VBDAs.


MATERIALS AND METHODS


PATIENT POPULATION

The present retrospective study was approved by the ethics committee of our
institution. Written informed consent for study inclusion was obtained from the
parents of all included patients. Between January 2016 and June 2018, 2,706
patients were referred to our department for endovascular treatment of an
intracranial aneurysm. Among this group, 153 patients were diagnosed with VBDAs,
and 54 patients agreed to undergo PED therapy. Of these 54 patients, four were
18 years old or younger at the time of presentation (two males, and two females;
mean age 9.25 years; age range 8–11 years). None of these four cases involved
traumatic aneurysms and/or collagen vascular disorders. Patient demographics and
clinical information collected from the medical records are shown in Table 1.


TABLE 1

Table 1. Patient demographics and clinical information on admission.





ENDOVASCULAR PROCEDURE

We selected endovascular treatment as the first choice for these pediatric
patients after comprehensive discussion within a comparatively full-scale group
of researchers including pediatric experts, neurologists, and radiologists. The
families of the patients also preferred endovascular treatment to open
neurosurgery, as this is a less invasive treatment. Thus, off-label use of the
PED was performed. All endovascular treatments were conducted by experienced
neuro-interventionists. All endovascular procedures were performed under general
anesthesia. After canalizing the femoral artery with a 6-F artery sheath, a 6-F
guiding catheter (Codman, Raynham, Massachusetts, USA) was placed in the distal
V2 segment. Marksman (EV3, Irvine, California, USA) was then navigated inside
the guiding catheter to the P2 segment of the posterior cerebral artery. Once
the PED reached the desired position, deployment was performed by a combination
of withdrawal of the Marksman catheter and advancement of the delivery wire. If
the diameter of the aneurysm or eccentric lumen exceeded 10 mm, we used the
jailing technique to coil the aneurysm or eccentric lumen with the assistance of
stents. Additional coiling was performed in three aneurysms through a pre-jailed
Echelon-10 catheter (EV3, Plymouth, Minnesota, USA) to loosely pack the
aneurysmal sac, or in vertebrobasilar junction (VBJ) aneurysms to sacrifice the
contralateral vertebral artery (VA). One patient underwent parent artery
occlusion using a balloon [Hyperform (EV3, Irvine, California, USA)]. If the
aneurysm originated from the basilar artery with abundant perforating arteries,
sole PED insertion may be considered the first choice to avoid the occurrence of
ischemic events.


ANTIPLATELET TREATMENT AND ANTICOAGULATION

All patients were premedicated with a dual antiplatelet regimen (1 mg/kg of
clopidogrel and 100 mg of aspirin daily) for 5 days prior to treatment. During
the procedure, an intravenous bolus dose of heparin (100 IU/kg) was
administered, and heparinization was continued to maintain an activated clotting
time of 2–3 times the baseline value throughout the procedure. Dual antiplatelet
therapy was continued for 6 months after the procedure, and aspirin was
continued for life, as per the standard embolism prophylaxis for intraluminal
stents.


RESULTS

We evaluated the patients' pre- and post-operative clinical statuses using the
modified Rankin scores (mRS), and evaluated the lesions after the procedure by
follow-up digital subtraction angiography (DSA) and magnetic resonance imaging
(MRI). One patient (25%) died from brainstem infarction or compression of the
brainstem 3 days after the procedure. The other three patients (75%) underwent
clinical and imaging follow-up 6 months after the procedure. Initial clinical
and radiographic data are summarized in Table 1, while follow-up data are
summarized in Table 2.


TABLE 2

Table 2. Angiographic and clinical follow-up data.





CLINICAL FOLLOW-UP

The pre- and post-operative mRS showed that the clinical presentations of three
patients (75%) (cases 1, 2, and 3) achieved excellent improvement. However, the
patient in case 4 died from brainstem infarction or compression of the brainstem
3 days after the insertion of four PEDs.


DIGITAL SUBTRACTION ANGIOGRAPHY FOLLOW-UP

DSA performed 6 months after the PED procedure showed that two patients (66.7%)
achieved favorable reconstruction of the parent vessel. Complete occlusion of
the parent artery was observed in one patient (33.3%) who had undergone
reconstructive endovascular treatment by two PEDs.


MAGNETIC RESONANCE IMAGING FOLLOW-UP

The comparison of MRI performed 6 months after the PED procedure with
preoperative MRI showed reduction of the mass effect in three patients (75%),
especially in case 3.


CASE DETAILS

CASE 1

A 10–12-year-old patient had experienced headaches and left-sided occipital pain
for 3 months without other neurological symptoms. Computed tomographic
angiography (CTA) performed at another hospital showed a giant left vertebral
dissecting aneurysm. The patient was then transferred to our center. DSA showed
a left vertebral dissecting aneurysm that measured 25 × 19 mm (Figures 1A,B),
and MRI revealed a severe mass effect. Due to the complexity of the aneurysm,
the decision was made to perform endovascular therapy with the PED. The patient
had a mRS of 1, and underwent intervention therapy with a PED (4.5 × 35 mm) and
coils (Figure 1C). The procedure was successful, with no complications.
Immediately postoperative angiography showed that the aneurysm was incompletely
occluded, with patency of the parent vessel (Figure 1D). After the procedure,
the clinical symptoms of patient were mildly improved compared with
preoperatively. At 6 months post-treatment, follow-up DSA demonstrated complete
aneurysmal occlusion and occlusion of the right VA (RVA) (Figures 1E,F).
Compared with preoperative MRI (Figure 1G), follow-up MRI (Figure 1H) showed a
reduction of the mass effect and increased space of the brainstem. At 6 months
after the procedure, the patient was neurologically normal, with a mRS of 0.


FIGURE 1

Figure 1. Images from a 10- to 12-year-old patient with a left vertebral
dissecting aneurysm (case 1). (A) Preoperative anteroposterior angiogram showing
a giant dissecting aneurysm in the LVA. (B) Preoperative anteroposterior
angiogram demonstrating the patency of the RVA. (C) Intraprocedural unsubtracted
view showing the location of the PED (4.5 × 35 mm). (D) Immediately
postoperative angiogram of the LVA demonstrating the reconstruction of the
parent vessel, and contrast stasis in the lumen of the aneurysm. (E,F) Six-month
post-treatment anteroposterior angiograms showing the patency of the LVA (E) and
the complete occlusion of the RVA (F). (G,H) Six-month post-treatment MRI (H)
compared with preoperative axial MRI (G) demonstrating reduction of the aneurysm
size (black arrow) and increased space around the brainstem (white arrow). LVA,
left vertebral artery; RVA, right vertebral artery; PED, pipeline embolization
device.




CASE 2

An 8–10-year-old patient had experienced headaches and diplopia for 3 weeks. At
another hospital, DSA showed a giant dissecting aneurysm located in the VBJ
(Figures 2A,B), and MRI demonstrated a conspicuous mass effect with a diameter
of 28 × 18 mm. The patient had a mRS of 1, and was transferred to our center for
endovascular therapy with the PED and coils. The RVA underwent endovascular
treatment with two PEDs (3.5 × 35 mm) (Figure 2C), while the left VA (LVA)
underwent endovascular treatment with distal balloon occlusion (Figure 2D).
Immediately postoperative angiography showed that the PEDs were inserted
successfully. After the procedure, the headache was mildly improved compared
with preoperatively. At 6 months post-treatment, follow-up DSA revealed that the
RVA had achieved excellent reconstruction (Figures 2E,F), and the LVA was
completely occluded. Follow-up MRI showed a reduction of the mass effect to a
diameter of 20 × 15 mm (Figures 2G,H). The patient made an excellent recovery,
with a mRS of 0.


FIGURE 2

Figure 2. Images from an 8- to 10-year-old patient with a giant dissecting
aneurysm located in the VBJ (case 2). (A,B) Preoperative anteroposterior
angiograms of the LVA (A) and RVA (B) showing a giant dissecting aneurysm in the
VBJ. (C) Intraprocedural unsubtracted view showing the successful insertion of
PEDs (3.5 × 35 mm) (black arrow). (D) Intraprocedural angiogram showing complete
occlusion of the LVA by a balloon (black arrow). (E,F) Six-month postoperative
angiograms showing the reconstruction of the RVA (E) and stable PEDs (F) (black
arrow). (G,H) Six-month postoperative MRI showing a mass effect with a diameter
of 20 × 15 mm (black arrow). VBJ, vertebrobasilar junction; LVA, left vertebral
artery; RVA, right vertebral artery; PED, pipeline embolization device.




CASE 3

An 8–10-year-old patient with a mRS of 2 experienced a sudden onset of headaches
accompanied by dysphagia 2 months before being admitted to our hospital. CTA
performed in another hospital revealed a giant dissecting aneurysm located in
the VBJ, which was confirmed on DSA performed in our hospital (Figures 3A,B).
The LVA was treated with two PEDs (3.5 × 35 mm), and the RVA underwent parent
artery occlusion with coils. Immediately postoperative angiography showed
excellent reconstruction of the LVA (Figure 3C), and complete occlusion of the
RVA (Figure 3D). After the procedure, the clinical symptoms were mildly improved
compared with preoperatively. One day post-treatment, MRI demonstrated a giant
mass effect with an intramural hematoma, resulting in severe brainstem
compression. Six months post-treatment, follow-up DSA revealed complete
occlusion of the LVA and RVA (Figures 3E,F). Compared with MRI performed at 1
day post-treatment (Figure 3G), follow-up MRI showed a marked reduction in the
mass effect (Figure 3H). At 6 months after the procedure, the patient had no
clinical problems and/or focal neurological function deficiency, with a mRS of
0. As this patient had weak dual posterior communicating arteries preoperatively
(Figures 3I,J), the good clinical outcome might be attributed to the presence of
robust dual posterior communicating arteries after the procedure (Figures 3K,L).


FIGURE 3

Figure 3. Images from an 8- to 10-year-old patient with a giant dissecting
aneurysm located in the VBJ (case 3). (A,B) Preoperative anteroposterior
angiograms of the LVA (A) and RVA (B) showing a giant dissecting aneurysm in the
VBJ. (C,D) Immediately postoperative lateral angiograms showing the successful
reconstruction of the LVA (C) and the complete occlusion of the RVA by coiling
(D). (E,F) Six-month post-treatment angiograms confirming the complete occlusion
of the LVA (E) and the RVA (F). (G,H) Six-month post-treatment MRI (H) compared
with MRI performed 1 day post-treatment (G) demonstrating the reduction in the
aneurysm size (black arrow) and increased space around the brainstem (white
arrow). (I,J) Preoperative angiograms of the left and right ICA demonstrating
weak dual-sided PCoAs. (K,L) Six-month post-treatment angiograms of the left and
right ICA confirming robust dual-sided PCoAs (black arrow) providing sufficient
blood for posterior circulation. VBJ, vertebrobasilar junction; LVA, left
vertebral artery; RVA, right vertebral artery; ICA, internal carotid artery;
PCoAs, posterior communicating arteries.




CASE 4

A 10–12-year-old patient experienced chronic headaches and vertigo for 8 months.
MRI performed in another hospital demonstrated a giant mass effect with an
intramural hematoma causing severe brainstem compression (Figures 4A,B). DSA
revealed a giant dissecting aneurysm located in the basilar artery (Figures
4C,D). The patient was then transferred to our center. Due to the large size of
this lesion, four PEDs (3.5 × 35 mm) were inserted to repair the wall of the
basilar artery (Figure 4E). The patient tolerated the procedure well.
Immediately postoperative angiography showed that the lumen of the aneurysm had
evident contrast stasis with the patency of the parent artery (Figures 4F,G).
One day post-treatment, the patient experienced an acute onset of dysphasia and
right hemiplegia; computed tomography (CT) was immediately performed and did not
show any significant findings (Figure 4H). The post-procedural symptoms were
thought be related to contrast neurotoxicity due to the large dosage of contrast
agent administered during the procedure, and so we did not perform repeat MRI.
The symptoms were gradually alleviated by rehydration therapy and symptomatic
treatment. At 3 days after the procedure, the patient had an acute onset of
headache and dizziness with loss of consciousness. While on the way to undergo
repeat CT, the patient became apneic. The patient was immediately transferred to
the Neurosurgical Intensive Care Unit, and underwent positive rescue treatments
of airway protection; however, the patient was unable to recover the ability to
self-breathe, lost consciousness, and died.


FIGURE 4

Figure 4. Images from a 10- to 12-year-old patient with a giant dissecting
aneurysm located in the basilar artery (case 4). (A,B) Preoperative MRI showing
a basilar giant dissecting aneurysm with compression of the brainstem (black
arrow). (C,D) Preoperative anteroposterior angiograms of the LVA (C) and RVA (D)
confirming a giant dissecting aneurysm located in the basilar artery. (E)
Intraprocedural unsubtracted view showing successful insertion of the PED (3.5 ×
35 mm) (black arrow). (F,G) Immediately postoperative anteroposterior angiograms
of the LVA (F) and RVA (G) demonstrating excellent reconstruction of the basilar
artery and evident contrast stasis in the lumen of the aneurysm. (H) CT
performed 1 day after the procedure confirming no indications of SAH. LVA, left
vertebral artery; RVA, right vertebral artery; PED, pipeline embolization
device; SAH, subarachnoid hematoma.





DISCUSSION

The PED technique is a new treatment modality for intracranial aneurysms,
particularly giant aneurysms, for which an excellent outcome cannot be achieved
via conditional endovascular treatment (6). Flow diversion is a new and
relatively untested technology in children, although the outcomes in adults are
promising. For challenging lesions in the pediatric population, flow diversion
may have a valuable role as a well-tolerated, safe treatment with durable
results (1). To date, few studies have confirmed the safety and effectiveness of
the PED technique in the treatment of pediatric giant dissecting aneurysms
located in the vertebrobasilar system, and most of the relevant literature is
comprised of case reports. Additionally, most published case reports only
describe successful examples, which may give misleading information on the
outcome of the PED technique. To objectively consider the feasibility and
effectiveness of the PED technique in this population, we described our early
experience with the PED technique in four consecutive pediatric patients.

The management of VBDAs is technically challenging due to their morphologic
features and localization (7). Giant vertebrobasilar aneurysms carry a high rate
of morbidity, and no treatment modality has yet significantly improved the
dismal natural history of the lesion (8). Furthermore, the treatment of
pediatric giant VBDAs is more complex, and there is minimal literature reporting
the management of this lesion. It is uncommon for a dissecting aneurysm to
resolve spontaneously or with medical treatment only (9). Hence, we need to
prevent the progression of these lesions, particularly in pediatric patients who
have longer expected lifespans than adults.

Microsurgical clipping of the aneurysm is the most effective method for
obliterating the aneurysm, and carries the lowest risk of recurrence (10).
However, there are two major limitations of this method for dissecting aneurysms
located in vertebrobasilar arteries. First, the aneurysm neck cannot be
identified for clipping, and the wall friability can make surgical clipping
difficult and risky (9). Second, the anatomic locations of these lesions
adjacent to the brainstem increase the difficulty of the surgical treatment,
with higher risks of mortality and morbidity (10). Thus, endovascular techniques
are preferred for these lesions (11–13). However, for these particular lesions,
traditional endovascular treatments (such coiling, stent-assisted coiling, and
balloon-assisted coiling) result in a high recurrence rate (14). Additionally,
pediatric patients can tolerate deconstructive treatment better than adults
because of a greater functional brain capacity and a better compensatory blood
supply (15–17). In the majority of reported cases in the pediatric population,
the chosen treatment for dissecting, fusiform, and giant partially thrombosed
aneurysms was parent vessel sacrifice (either surgically or endovascularly),
with good clinical results (18–20). However, in situations in which parent
artery preservation is mandatory given the expected long life spans of children
and the branches of the vessels, the use of stent-assisted techniques may be the
most appropriate choice (21). Thus, endovascular treatment via the insertion of
a PED may be a viable alternative.

Currently, a significant proportion of intracranial aneurysms in adults are
successfully treated with flow diverters. Flow diverters have also emerged as an
effective and safe alternative in small case series, which report favorable
outcomes in young children (17), particularly for VBDAs. To the best of our
knowledge, there have only been seven reported cases (seven aneurysms) of PED
insertion in children with VBDAs, including four giant aneurysms, two large
aneurysms, and one small aneurysm (6, 17, 22–25) (Table 3). The literature
indicates that the use of flow diverters in children is considered positive,
particularly for VBDAs; hence, the treatment modalities for these lesions have
gradually shifted from parent artery occlusion to the PED technique. Similar to
the current literature, we report acceptable therapeutic outcomes for these
complex lesions; although one patient died from brainstem compression or
infarction, the other patients were able to resume normal life without major
neurological deficiency. Additionally, it was crucial to determine whether the
mass effect resulting from these complex lesions could be alleviated compared
with the pretreatment status. We confirmed that the mass effect in the three
surviving patients was reduced on follow-up MRI, in accordance with previous
case reports (17, 22, 23, 26).


TABLE 3

Table 3. Literature summary of the use of the PED technique for pediatric
vertebrobasilar dissecting aneurysms.




Although the PED technique was approved by the Food and Drug Administration in
2011 for the treatment of large or giant wide-necked anterior circulation
aneurysms in the internal carotid artery from the petrous to the superior
hypophyseal segments in adults (27), the use of the PED technique for pediatric
dissecting aneurysms was off-label. This approach was applied to this particular
population after a multidisciplinary discussion, under the condition that
conservative therapeutic methods could not achieve a good outcome. Furthermore,
from a morphometric standpoint, we found that the size range of currently
available intracranial stents or flow diverters is sufficient to cover the
pediatric population, and intracranial arterial diameters in children do not
undergo extensive growth, especially after early childhood (28). Hence,
endovascular treatment with PEDs may become a feasible choice for pediatric
complex lesions, such as giant VBDAs.

In our case series, follow-up DSA showed that case 3 had complete occlusion of
the LVA at 6 months post-treatment. We consider that the cause of this parent
vessel complete occlusion might have been an in-stent thrombus. Thus, strict
attention must be paid to pre- or post-procedural antiplatelet medication
protocols for flow diverters. There is no standard antiplatelet/anticoagulant
therapy for children undergoing intracranial placement of vascular scaffolds
(such as stents, stent grafts, or flow diverters) (28), and antiplatelet
administration for endovascular treatment is extremely variable (29–31).
Furthermore, the antiplatelet/anticoagulant therapy for adults undergoing PED
insertion for aneurysms in the posterior circulation is also variable (32–34).
In children, a weight-based dose of 0.2–1 mg/kg/day is associated with a 43%
platelet aggregation inhibition response. However, weight-based dose
calculations extrapolated from an adult dosage of 75 mg of clopidogrel per day
are not only misleading, but may also lead to life-threatening consequences (35,
36). Some previously reported cases experienced thrombotic complications and
hemorrhagic events because of inappropriate antiplatelet therapy (24, 37, 38).
It is important to be aware of the different sensitivity of each child to the
dual antiplatelet regimen. Furthermore, there is a need for age-specific
reference ranges (39). In this particular population, initiating appropriate
antiplatelet therapy before and after treatment could minimize the risks of
hemorrhage and ischemic events as a result of parent artery occlusion and
in-stent stenosis.

The patient in case 4 died 3 days after the procedure, although this patient
tolerated the procedure well and CT showed no signs of subarachnoid hematoma.
Multidisciplinary discussion by many experts attributed the death to two
potential causes: severe compression of the brainstem due to acute thrombosis,
or brainstem infarction associated with acute thrombosis in the stent. The
parents of the patient did not consent to an autopsy to confirm the cause of
death. A risk-benefit evaluation must be considered before selecting a treatment
modality for pediatric patients with a severe mass effect or large intracranial
hematoma. Although the parents of the patient in case 4 refused a surgical
operation, surgical treatment with an artery bypass may have been an alternative
method. A multidisciplinary approach to managing aneurysms facilitates the
attainment of good outcomes in this diverse and challenging group of patients.


LIMITATIONS

As pediatric giant VBDAs are rare, the present study was only able to include
four cases. Additionally, although long-term follow-up is important in this
special population that appears to be at greater risk of delayed complications,
follow-up was limited to an average of 6 months. Moreover, we did not check the
aspirin and Plavix response before and after procedure, which is an important
measure to reduce the risk of ischemic and/or hemorrhagic events. Finally, there
was a lack of suitable controlled patients treated via other therapeutic
methods. A prospective, multicenter investigation with a large sample is
essential.


CONCLUSIONS

PEDs could be feasible in the treatment of pediatric giant VBDAs. However, the
safety and efficacy of this method have not been clarified in this special
population, and long-term follow-up is still necessary.


AUTHOR CONTRIBUTIONS

JW and YZ performed the manuscript writing. ZT, LJ, WZ, WL, JC, XD, ZW, and KW
acquired the data. JL, PL, ZM, and YZ analyzed and interpreted the data. ML and
XY conceived and designed the research, and handled funding and supervision.


FUNDING

This work was supported by National Key Research and Development Plan of China
(grant number: 2016YFC1300800), the National Natural Science Foundation of China
(grant numbers: 81220108007, 81801156, 81801158, 81471167 and 81671139) and the
Special Research Project for Capital Health Development (grant number:
2018-4-1077).


CONFLICT OF INTEREST STATEMENT

The authors declare that the research was conducted in the absence of any
commercial or financial relationships that could be construed as a potential
conflict of interest.


REFERENCES

1. Ramon N, Brown BL, Alexandra B, Nathan R, Philipp A, Hanel RA. Flow diversion
for complex intracranial aneurysms in young children. J Neurosurg Pediatr.
(2015) 15:276–81. doi: 10.3171/2014.9.PEDS14333

CrossRef Full Text | Google Scholar

2. Zhang YS, Wang S, Wang Y, Tian ZB, Liu J, Wang K, et al. Treatment for
spontaneous intracranial dissecting aneurysms in childhood: a retrospective
study of 26 cases. Front Neurol. (2016) 7:224. doi: 10.3389/fneur.2016.00224

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Yap L, Patankar T, Pysden K, Tyagi A, Goddard T. Spontaneous dissecting
lenticulostriate artery aneurysm in children. J Child Neurol. (2014) 30:1060–4.
doi: 10.1177/0883073814541477

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Debette S, Compter A, Labeyrie MA, Uyttenboogaart M, Metso TM, Majersik JJ,
et al. Epidemiology, pathophysiology, diagnosis, and management of intracranial
artery dissection. Lancet Neurol. (2015) 14:640–54. doi:
10.1016/S1474-4422(15)00009-5

PubMed Abstract | CrossRef Full Text | Google Scholar

5. Sanai N, Quinoneshinojosa A, Gupta NM, Perry V, Sun PP, Wilson CB, et al.
Pediatric intracranial aneurysms: durability of treatment following
microsurgical and endovascular management. J Neurosurg. (2006) 104:82–9. doi:
10.3171/ped.2006.104.2.3

PubMed Abstract | CrossRef Full Text | Google Scholar

6. D'Urso PI, Lanzino G, Cloft HJ, Kallmes DF. Flow diversion for intracranial
aneurysms a review. Stroke. (2011) 118:2363–8. doi: 10.1161/STROKEAHA.111.620328

CrossRef Full Text | Google Scholar

7. Fiorella D, Albuquerque FC, Deshmukh VR, Woo HH, Rasmussen PA, Masaryk TJ, et
al. Endovascular reconstruction with the Neuroform stent as monotherapy for the
treatment of uncoilable intradural pseudoaneurysms. Neurosurgery. (2006) 59:291.
doi: 10.1227/01.NEU.0000223650.11954.6C

PubMed Abstract | CrossRef Full Text | Google Scholar

8. Victor A. Surgical treatment of complex intracranial aneurysms. In:
Moldo-Romanian Neurosurgical Simposium (2015).

Google Scholar

9. Faria DBM, Castro RN, Lundquist J, Scrivano E, Ceratto R, Ferrario A, et al.
The role of the pipeline embolization device for the treatment of dissecting
intracranial aneurysms. Am J Neuroradiol. (2011) 32:2192–5. doi:
10.3174/ajnr.A2671

CrossRef Full Text | Google Scholar

10. Mgz G, Srinivasan VM, Cherian J, Wagner KM, Chen SR, Johnson J, et al.
Multimodal treatment of intracranial aneurysms in children: clinical case series
and review of the literature. World Neurosurg. (2017) 111:e294–307. doi:
10.1016/j.wneu.2017.12.057

CrossRef Full Text | Google Scholar

11. Halbach VV, Higashida RT, Dowd CF, Fraser KW, Smith TP, Teitelbaum GP, et
al. Endovascular treatment of vertebral artery dissections and pseudoaneurysms.
J Neurosurg. (1993) 79:183–91. doi: 10.3171/jns.1993.79.2.0183

PubMed Abstract | CrossRef Full Text | Google Scholar

12. Jin YJ, Ahn JY, Chung YS, Han IB, Sang SC, Yoon PH, et al. Treatment of
intra- and extracranial arterial dissections using stents and embolization.
Cardiovasc Intervent Radiol. (2005) 28:595–602. doi: 10.1007/s00270-004-0199-x

CrossRef Full Text | Google Scholar

13. Vasan R, Patel J, Sweeney JM, Carpenter AM, Downes K, Youssef AS, et al.
Pediatric intracranial aneurysms: current national trends in patient management
and treatment. Child Nerv Syst. (2013) 29:451. doi: 10.1007/s00381-012-1945-z

PubMed Abstract | CrossRef Full Text | Google Scholar

14. Kim BM, Shin YS, Kim SH, Suh SH, Ihn YK, Kim DI, et al. Incidence and risk
factors of recurrence after endovascular treatment of intracranial
vertebrobasilar dissecting aneurysms. Stroke. (2011) 42:2425. doi:
10.1161/STROKEAHA.111.617381

PubMed Abstract | CrossRef Full Text | Google Scholar

15. Proust F, Toussaint P, Garniéri J, Hannequin D, Legars D, Houtteville JP, et
al. Pediatric cerebral aneurysms. J Neurosurg. (2001) 94:733–9. doi:
10.3171/jns.2001.94.5.0733

PubMed Abstract | CrossRef Full Text | Google Scholar

16. Ferrante L, Fortuna A, Celli P, Santoro A, Fraioli B. Intracranial arterial
aneurysms in early childhood. Surg Neurol. (1988) 29:39. doi:
10.1016/0090-3019(88)90122-X

PubMed Abstract | CrossRef Full Text | Google Scholar

17. Cunegatto-Braga M, Hogan B, Aguilar-Salinas P, Beier AD, Hanel RA. Pipeline
embolization device flow diversion for a dissecting ruptured posterior cerebral
artery aneurysm in a pediatric patient. World Neurosurg. (2018) 117:255–60. doi:
10.1016/j.wneu.2018.06.031

PubMed Abstract | CrossRef Full Text | Google Scholar

18. Saraf R, Shrivastava M, Siddhartha W, Limaye U. Intracranial pediatric
aneurysms: endovascular treatment and its outcome. J Neurosurg Pediatr. (2012)
10:230–40. doi: 10.3171/2012.5.PEDS1210

PubMed Abstract | CrossRef Full Text | Google Scholar

19. Hetts SW, Narvid J, Sanai N, Lawton MT, Gupta N, Fullerton HJ, et al.
Intracranial aneurysms in childhood: 27-year single-institution experience. Am J
Neuroradiol. (2009) 30:1315. doi: 10.3174/ajnr.A1587

PubMed Abstract | CrossRef Full Text | Google Scholar

20. Lv X, Jiang C, Li Y, Yang X, Wu Z. Endovascular treatment for pediatric
intracranial aneurysms. Neuroradiology. (2009) 51:749–54. doi:
10.1007/s00234-009-0553-4

PubMed Abstract | CrossRef Full Text | Google Scholar

21. Wakhloo AK, Mandell J, Gounis MJ, Brooks C, Linfante I, Winer J, et al.
Stent-assisted reconstructive endovascular repair of cranial fusiform
atherosclerotic and dissecting aneurysms: long-term clinical and angiographic
follow-up. Stroke. (2008) 39:3288–96. doi: 10.1161/STROKEAHA.107.512996

PubMed Abstract | CrossRef Full Text | Google Scholar

22. Anna Z, Benjamin G, Francis T. Implantation of two flow diverter devices in
a child with a giant, fusiform vertebral artery aneurysm: case report. Pediatr
Neurol. (2013) 50:185–7. doi: 10.1016/j.pediatrneurol.2013.09.014

CrossRef Full Text | Google Scholar

23. Mohammad LM, Coon AL, Carlson AP. Resolution of giant basilar artery
aneurysm compression and reversal of sensorineural hearing loss with use of a
flow diverter: case report. J Neurosurg Pediatr. (2017) 20:81. doi:
10.3171/2016.9.PEDS16428

PubMed Abstract | CrossRef Full Text | Google Scholar

24. Vargas SA, Diaz C, Herrera DA, Dublin AB. Intracranial aneurysms in
children: the role of stenting and flow-diversion. J Neuroimaging. (2016) 26:41.
doi: 10.1111/jon.12305

PubMed Abstract | CrossRef Full Text | Google Scholar

25. Fiorella D, Kelly ME, Albuquerque FC, Nelson PK. Curative reconstruction of
a giant midbasilar trunk aneurysm with the pipeline embolization device.
Neurosurgery. (2009) 64:212–7. doi: 10.1227/01.NEU.0000337576.98984.E4

PubMed Abstract | CrossRef Full Text | Google Scholar

26. Szikora I, Marosfoi M, Salomváry B, Berentei Z, Gubucz I. Resolution of mass
effect and compression symptoms following endoluminal flow diversion for the
treatment of intracranial aneurysms. Am J Neuroradiol. (2013) 34:935–9. doi:
10.3174/ajnr.A3547

PubMed Abstract | CrossRef Full Text | Google Scholar

27. Lopes DK, Jang DK, Cekirge S, Fiorella D, Hanel RA, Kallmes DF, et al.
Morbidity and mortality in patients with posterior circulation aneurysms treated
with the pipeline embolization device: a subgroup analysis of the international
retrospective study of the pipeline embolization device. Neurosurgery. (2017)
83:488–500. doi: 10.1093/neuros/nyx467

PubMed Abstract | CrossRef Full Text | Google Scholar

28. Barburoglu M, Arat A. Flow diverters in the treatment of pediatric
cerebrovascular diseases. Am J Neuroradiol. (2016) 38:113–8. doi:
10.3174/ajnr.A4959

PubMed Abstract | CrossRef Full Text | Google Scholar

29. Takemoto K, Tateshima S, Golshan A, Gonzalez N, Jahan R, Duckwiler G, et al.
Endovascular treatment of pediatric intracranial aneurysms: a retrospective
study of 35 aneurysms. J Neurointervent Surg. (2014) 6:432–8. doi:
10.1136/neurintsurg-2013-010852

PubMed Abstract | CrossRef Full Text | Google Scholar

30. Appelboom G, Kadri K, Hassan F, Leclerc X. 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. doi:
10.1227/01.NEU.0000365370.82554.08

PubMed Abstract | CrossRef Full Text | Google Scholar

31. Burrows AM, Zipfel G, Lanzino G. New devices: treatment of a pediatric
recurrent fusiform middle cerebral artery (MCA) aneurysm with a flow diverter. J
Neurointervent Surg. (2013) 5:e47. doi: 10.1136/neurintsurg-2012-010478.rep

CrossRef Full Text

32. Albuquerque FC, Min SP, Abla AA, Crowley RW, Ducruet AF, Mcdougall CG. A
reappraisal of the Pipeline embolization device for the treatment of posterior
circulation aneurysms. J Neurointervent Surg. (2015) 7:641–5. doi:
10.1136/neurintsurg-2014-011340

PubMed Abstract | CrossRef Full Text | Google Scholar

33. Liang F, Zhang Y, Guo F, Zhang Y, Yan P, Liang S, et al. Use of pipeline
embolization device for posterior circulation aneurysms: single-center
experiences with comparison with anterior circulation aneurysms. World
Neurosurg. (2018) 112:e683. doi: 10.1016/j.wneu.2018.01.129

PubMed Abstract | CrossRef Full Text | Google Scholar

34. Kühn AL, Kan P, Massari F, Lozano JD, Hou SY, Howk M, et al. Endovascular
reconstruction of unruptured intradural vertebral artery dissecting aneurysms
with the Pipeline embolization device. J Neurointervent Surg. (2015) 8:1048–51.
doi: 10.1136/neurintsurg-2015-012028

PubMed Abstract | CrossRef Full Text

35. Mertens L, Eyskens B, Boshoff D, Gewillig M. Safety and efficacy of
clopidogrel in children with heart disease. J Pediatr. (2008) 153:61–4. doi:
10.1016/j.jpeds.2007.12.050

PubMed Abstract | CrossRef Full Text | Google Scholar

36. Li JS, Yow E, Berezny KY, Bokesch PM, Takahashi M, Graham TP Jr, et al.
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) 117:553. doi: 10.1161/CIRCULATIONAHA.107.715821

PubMed Abstract | CrossRef Full Text | Google Scholar

37. Abla AA, Zaidi HA, Crowley RW, Britz GW, Mcdougall CG, Albuquerque FC, et
al. Optic chiasm compression from mass effect and thrombus formation following
unsuccessful treatment of a giant supraclinoid ICA aneurysm with the Pipeline
device: open surgical bailout with STA-MCA bypass and parent vessel occlusion. J
Neurosurg Pediatr. (2014) 14:31–7. doi: 10.3171/2014.4.PEDS13213

PubMed Abstract | CrossRef Full Text | Google Scholar

38. Cobb MIH, Zomorodi AR, Hauck EF, Smith TP, Gonzalez LF. Optimal pediatric
dosing of anti-platelet agents for pipeline stent embolization—a case report and
review of the literature. Child Nerv Syst. (2017) 33:1–6. doi:
10.1007/s00381-016-3311-z

CrossRef Full Text | Google Scholar

39. Yip C, Linden MD, Attard C, Monagle P, Ignjatovic V. Platelets from children
are hyper-responsive to activation by thrombin receptor activator peptide and
adenosine diphosphate compared to platelets from adults. Br J Haematol. (2015)
168:526–32. doi: 10.1111/bjh.13153

PubMed Abstract | CrossRef Full Text | Google Scholar



Keywords: pediatric, dissecting, giant, vertebrobasilar, pipeline

Citation: Wang J, Zhang Y, Lv M, Yang X, Tian Z, Liu J, Liu P, Miao Z, Jia L,
Chen J, Ding X, Zhang Y, Zhu W, Li W, Wang K and Wang Z (2019) Application of
the Pipeline Embolization Device for Giant Vertebrobasilar Dissecting Aneurysms
in Pediatric Patients. Front. Neurol. 10:179. doi: 10.3389/fneur.2019.00179

Received: 08 December 2018; Accepted: 12 February 2019;
Published: 11 March 2019.

Edited by:

Diogo C. Haussen, Emory University, United States

Reviewed by:

Viktor Szeder, UCLA David Geffen School of Medicine, United States
Waldo Rigoberto Guerrero, Aurora St. Luke's Medical Center, United States

Copyright © 2019 Wang, Zhang, Lv, Yang, Tian, Liu, Liu, Miao, Jia, Chen, Ding,
Zhang, Zhu, Li, Wang and Wang. This is an open-access article distributed under
the terms of the Creative Commons Attribution License (CC BY). The use,
distribution or reproduction in other forums is permitted, provided the original
author(s) and the copyright owner(s) are credited and that the original
publication in this journal is cited, in accordance with accepted academic
practice. No use, distribution or reproduction is permitted which does not
comply with these terms.

*Correspondence: Ming Lv, dragontiger@163.com
Xinjian Yang, yangxinjian@voiceoftiantan.org

†These authors share first authorship



Disclaimer: All claims expressed in this article are solely those of the authors
and do not necessarily represent those of their affiliated organizations, or
those of the publisher, the editors and the reviewers. Any product that may be
evaluated in this article or claim that may be made by its manufacturer is not
guaranteed or endorsed by the publisher.




FOOTER

 * Guidelines
   
   
    * Author guidelines
    * Editor guidelines
    * Policies and publication ethics
    * Fee policy

 * Explore
   
   
    * Articles
    * Research Topics
    * Journals

 * Outreach
   
   
    * Frontiers Forum
    * Frontiers Policy Labs
    * Frontiers for Young Minds

 * Connect
   
   
    * Help center
    * Emails and alerts
    * Contact us
    * Submit
    * Career opportunities

Follow us
© 2024 Frontiers Media S.A. All rights reserved
Privacy policy | Terms and conditions
Download article
Download
 * Download PDF
 * ReadCube
 * EPUB
 * XML (NLM)


Otomatik - 13.107.246.44 CloudFlare DNS Türk Telekom DNS Google DNS Open DNS
OSZAR »

X (2)
Mendeley (12)
See more details





WE USE COOKIES

Our website uses cookies that are essential for its operation and additional
cookies to track performance, or to improve and personalize our services. To
manage your cookie preferences, please click Cookie Settings. For more
information on how we use cookies, please see ourCookie Policy
Cookies Settings Reject non-essential cookies Accept cookies



PRIVACY PREFERENCE CENTER

Our website uses cookies that are necessary for its operation. Additional
cookies are only used with your consent. These cookies are used to store and
access information such as the characteristics of your device as well as certain
personal data (IP address, navigation usage, geolocation data) and we process
them to analyse the traffic on our website in order to provide you a better user
experience, evaluate the efficiency of our communications and to personalise
content to your interests. Some cookies are placed by third-party companies with
which we work to deliver relevant ads on social media and the internet. Click on
the different categories' headings to change your cookie preferences. If you
wish to learn more about how we use cookies, please see our cookie policy below.
Cookie Policy
Allow all


MANAGE CONSENT PREFERENCES

STRICTLY NECESSARY COOKIES

Always Active

These cookies are necessary for our websites to function as they enable you to
navigate around the sites and use our features. They cannot be switched off in
our systems. They are activated set in response to your actions such as setting
your privacy preferences, logging-in or filling in forms. You can set your
browser to block or alert you about these cookies, but some parts of the site
will not then work.

PERFORMANCE/ANALYTICS COOKIES

Performance/Analytics Cookies

These cookies allow us to collect information about how visitors use our
website, including the number of visitors, the websites that referred them to
our website, and the pages that they visited. We use them to compile reports, to
measure and improve the performance of our website, analyze which pages are the
most viewed, see how visitors move around the site and fix bugs. If you do not
allow these cookies, your experience will not be altered but we will not be able
to improve the performance and content of our website.

FUNCTIONAL COOKIES

Functional Cookies

These cookies enable our website to supply enhanced functionality and
personalization and remember your preferences. They may be set by us or by third
party providers whose services we have added to our pages, including social
media platforms. If you do not allow these cookies, some of these services may
not function properly, or you may not be able to view certain social media
content available on our websites. 

TARGETING/ADVERTISING COOKIES

Targeting/Advertising Cookies

These cookies may be set by us to offer your personalized content and
opportunities to cooperate. They may also be used by social media companies we
work with to build a profile of your interests and show you relevant adverts on
their services. They do not store directly personal information but are based on
unique identifiers related to your browser and internet device. If you do not
allow these cookies, you will experience less targeted advertising. 

Back Button


COOKIE LIST



Search Icon
Filter Icon

Clear
checkbox label label
Apply Cancel
Consent Leg.Interest
checkbox label label
checkbox label label
checkbox label label

Confirm My Choices