DOI: https://doi.org/10.21203/rs.3.rs-2852364/v1
Objective
Cerebral vasospasm, or delayed cerebral ischemia (DCI), is a subarachnoid hemorrhage complication that increases morbidity and mortality. DCI treatment with balloon percutaneous transluminal angioplasty (PTA) in adults is well known, but data in preschool children are scarce because of its rarity. In addition, the smaller diameters and fragility of the vessels in childhood might lead to complications. This study presents two cases of DCI in children treated with balloon angioplasty. Therefore, it may contribute to a better understanding of the role of PTA as an effective treatment modality in this population.
Methods
Two children (3 and 5-year-old) with DCI were treated with balloon PTA after aneurysmal subarachnoid hemorrhage.
Results
Both patients survived without complications or new infarction.
Conclusions
Balloon angioplasty for proximal DCI may improve clinical outcomes in selected pediatric patients. Further studies are needed to clarify the best candidates, materials and techniques.
Cerebral vasospasm, also called delayed cerebral ischemia (DCI), is a common complication of subarachnoid hemorrhage (SAH) [14]. In most cases, DCI begins four days after bleeding, the narrowing is maximal at 6–8 days, and it resolves up to 2–3 weeks after bleeding [5]. Although well characterized in aneurysmal SAH, DCI can occur after hemorrhage due to trauma, arteriovenous malformations (AVM), tumors, coagulopathies, vasculitis, and intracranial surgeries [5, 7, 14, 15]. DCI is rare in childhood but can lead to severe neurological deficits or death [7, 14]. In addition, data is lacking to establish treatment recommendations and reduce risks for children. We present two cases of severe symptomatic vasospasm successfully treated by balloon percutaneous transluminal angioplasty (PTA).
A 3-year-old girl with vomiting, decreased consciousness and headache, was intubated at hospital admission. The neuroimage studies showed circumferential brainstem mass, with SAH and intraventricular hemorrhage causing obstructive hydrocephalus. After emergency external ventricular drain, MRI diagnosticated a giant vertebrobasilar aneurysm (6 x 4mm). The uneventful endovascular treatment with parent vessel occlusion achieved good result, and she was extubated on second day after bleeding, without any deficits. However, in 11th day she presented with convulsive state and decerebration, and the MRI showed cerebral watershed ischemia due to bilateral internal carotid artery (ICA) vasospasm. The angiogram evidenced bilateral ICA stenosis, then balloon PTA was rapidly performed using a balloon 3x10 mm HyperGlide™ (Medtronic, Minneapolis, MN, USA), achieving diameter normalization. She was discharged on the 21st day with mild cognitive impairment and ataxia. Progressive recovery occurred during a 1-year outpatient follow-up, and late MRI showed mass reduction (Fig. 1).
A 5-year-old boy presented with a sudden headache, somnolence, and right hemiparesis. The CT scan showed SAH, intraventricular, and left temporal intraparenchymal hemorrhage. The angiogram evidenced a ruptured aneurysm in the distal left posterior cerebral artery, which was occluded with coils. The postoperative course evolved without deficits, and etiologic investigation ruled out an infectious aneurysm. On the 7th day, he presented aphasia and right hemiplegia, and CT scan ruled out rebleeding and hydrocephalus. The MRI showed diffusion restriction in the left cerebral hemisphere, while an angiogram confirmed severe vasospasm. In the same procedure, a PTA using a 4x20 mm HyperGlide™ (Medtronic, Minneapolis, MN, USA) balloon performed in proximal vessels improved the arterial diameter. After tracheostomy and gastrostomy, he was discharged aphasic and hemiplegic on the 33rd day. After 18 months of rehabilitation, he had mild aphasia, hemiparesia and could walk independently. The follow-up CT scan showed gliosis in the ischemic area (Fig. 2).
Aneurysmal SAH is rare in childhood [5], and the reported incidence of associated DCI in children is around 25% − 53% [4, 10, 13, 17]. Cerebral vasospasm’s is usual definition is an arterial diameter reduction greater than 50% compared to admission diameter on brain imaging [7]. However, other authors define DCI as the sudden onset of neurological deficit, transient or not, associated with angiographic confirmation of vessel narrowing in the corresponding territory [4]. The physiopathology of DCI involves several mechanisms that decrease cerebral blood flow (CBF) and lead to tissue ischemia and cerebral infarction [2, 7]. Transcranial Doppler (TCD) monitoring helps to detect vasospasm, especially in sedated or comatose patients, and a recent consensus stated recommendations for children [12]. In our cases, the TCD was not available, thus delayed diagnosis may have worsened the clinical outcomes.
Even without medical treatment, DCI usually has better outcomes in children than adults, probably due to collateral circulation. However, there are no specific guidelines for managing DCI in children, with only a few descriptions in the literature [7, 14]. Therefore, physicians often adapt adult treatment guidelines to pediatric patients [10]. The initial step after suspicion of DCI is usually medical treatment. Still, pediatric features are distinct from adults: a study concluded that oral nimodipine in children did not eliminate vasospasm, rebleeding or infarction, but produced significant hypotension [5]. Besides that, continuous intravenous infusion of milrinone in children might improve vasospasm [7]. In adults, refractory cases of symptomatic DCI are usually treated through endovascular therapy [2]. Although there is a lack of controlled randomized trials, multiple published case series demonstrated the efficacy and safety of balloon PTA to recover neurological deficits and prevent further ischemic insults [2]. This technique achieves far better results when compared to the natural history of the disease: 92% of patients with intractable DCI treated with balloon PTA improved neurologically, with increased cerebral blood flow demonstrated with xenon-enhanced CT studies in all cases [3]. Although the ideal timing for intervention remains unclear, treatment should likely be performed as early as possible. A 2-hour window for restoration of cerebral blood flow might be associated with better chances for improved outcomes [16].
The balloon PTA appears to have more long-lasting effects than pharmacological treatment, probably related to disruption of vessel wall architecture, affecting especially the collagen fibers and the medial layer components [2]. Although strong radial force and balloon diameter accuracy are key features for treating atherosclerotic lesions, intracranial vasospasm requires slow inflation under lower pressure [11]. The neurovascular balloons should be compliant, flexible, less traumatic, having also small profile and low pressure. Those characteristics improve vessel navigation and decrease the risk of vessel rupture. Although most of the current devices were designed for balloon test occlusion and balloon-assisted aneurysm coiling, they can be safely used for dilatation of stenosis in the cerebral arteries in order to improve perfusion. The recommended balloon inflation is with 50:50 contrast-saline solution to enable safe visualization. As they tend to have a relatively large maximum inflation diameter, these balloons need to be keenly observed, and inflation must cease once the balloon starts to conform to the vessel lumen. The balloon is usually inflated with a highly calibrated threaded 1-ml syringe to enable adjustments in the 0.01-ml range, because its inflated diameter is calibrated to the injected volume. Hence, control of the volume injection allows better angiographic and clinical outcomes.
Even in adults, balloon PTA is often limited to proximal vessels, bigger than 2–3 mm [2]. That includes the distal ICA (mean diameter: 3.68 mm), basilar artery, M1 segment of the middle cerebral artery (MCA, mean diameter: 2.68 mm), A1 segment of the anterior cerebral artery (ACA, mean diameter: 2.3 mm), and P1 segment of the posterior cerebral artery [1]. The smaller diameters and vessel fragility in the pediatric population may increase the risk of arterial injury or rupture and may also preclude using most guide catheters and transluminal devices [17]. Nevertheless, MCA reaches almost its full diameter at the 6 months of life, while ICA and ACA approximately have an adult diameter by the age of 4 years [1]. Indeed, Pendharkar et al. [14] already performed a successful balloon PTA for DCI after arteriovenous malformation rupture in a 13-year-old boy. In addition, Kellner et al. [9] carried out a balloon PTA for DCI due to SAH in a 14-year-old boy with Loeys–Dietz syndrome. For infants and smaller children, however, data is scarce. Snelling et al. [17] performed mechanical angioplasty in an infant with DCI using a mechanical dilatation with a microcatheter and a microguidewire because balloon PTA could not be safe.
The overall risk of complication of balloon PTA is approximately 5%, including a 1% risk of vessel perforation/rupture, usually fatal [6]. Additional complications of balloon PTA include thrombosis, embolism, reperfusion injury, and displacement of surgical clips [2]. Jestaedt et al. [8] found a significant difference during the treatment of severe angiographic vasospasm: infarction occurred in only 7% of MCA territories treated with balloon PTA compared to 38% of ACA territories not subjected to angioplasty.
The present study has all limitations of a single-center retrospective study, and evaluating only two children preclude definitive statements. In addition, the performed angioplasty exceeding the two-hours-window should have limited the optimal response, and no objective pre- and post-operative perfusion studies were performed.
Aggressive neuromonitoring is recommended to diagnose cerebral vasospasm early, and balloon PTA may contribute to DCI management and improve outcomes of selected pediatric patients. Multicentric trials are needed to guide the further selection of DCI therapies and inform age-adjusted preventive or therapeutic modifications.
Ethical Approval: The study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki and followed the ICMJE Recommendations for the Protection of Research Participants. This study was approved by the Ethics Committee of Hospital de Crianças César Pernetta and Hospital Pequeno Príncipe. Written informed consent for publication was achieved and signed by the patients’ surrogates. All patients’ identifications were removed to preserve anonymity.
Competing interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Authors' contributions: Z.D.J., R.M.R., F.R. and A.K.M.: conception of the work and acquisition of the data. L.A.F., C.A.M., and A.C.D.: analysis and interpretation of the data. Z.D.J.: drafting of the work; R.M.R., A.K.M., F.R., L.A.F., A.N.F., and A.C.D.: critically revising the work for intellectual content. Z.D.J., R.M.R., A.K.M., F.R., L.A.F., C.A.M., and A.C.D.: final approval of the version to be published. Z.D.J., R.M.R., A.K.M., F.R., L.A.F., C.A.M., and A.C.D.: accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding: No targeted funding reported.
Availability of data and materials: All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.
Acknowledgements: We thank to Ms. Maiara Milena Rosa for her technical help.