Balloon angioplasty for cerebral vasospasm in preschool children

Abstract

Background

Subarachnoid hemorrhage evolving with cerebral vasospasm and delayed cerebral ischemia may increase morbidity and mortality. Treating vasospasm with balloon percutaneous angioplasty (PTA) in adults is well known, but data in preschool children are scarce. In addition, the smaller diameters and fragility of the vessels in childhood might lead to serious complications. This study presents two cases of cerebral vasospasm in preschool children treated with balloon PTA. Therefore, it may contribute to a better understanding of the role of that technique as an effective treatment modality in this population.

Methods

Balloon PTA was performed in two children (3 and 4 year-old) with aneurysmal subarachnoid hemorrhage and delayed cerebral ischemia.

Results

The procedures were uneventful, and both patients survived without complications or new infarction.

Conclusions

Balloon PTA for proximal vasospasm may improve clinical outcomes in selected pediatric patients. Further studies are needed to clarify the best candidates, materials, and techniques.

Introduction

Delayed cerebral ischemia (DCI) and symptomatic vasospasm are severe subarachnoid hemorrhage (SAH) complications. ¹ The vasospasm typically begins 4 days post-SAH, peaks at 6 to 8 days, and resolves up to 2 to 3 weeks. ² Besides aneurysmal SAH, the vasospasm can also occur after hemorrhage due to trauma, arteriovenous malformations, tumors, coagulopathies, intracranial surgeries, meningitis, and vasculitis.^1–4 Although vasospasm and DCI are rare in childhood, it can lead to severe neurological deficits or death.^1,4 Because data is lacking to establish treatment recommendations and reduce risks for children, we present two successfully treated cases of severe DCI in preschool patients.

Methods

This study was approved by the institutional Ethics Committee. Written informed consent for publication was achieved and signed by the patients’ surrogates.

Case 1

A 3-year-old girl with headache and vomiting, decreased consciousness, Glasgow coma scale (GCS) 12, Hunt-Hess scale grade III, World Federation of Neurosurgical Societies (WFNS) scale grade IV, was intubated at hospital admission. The neuroimage studies showed circumferential brainstem mass, with SAH and intraventricular hemorrhage causing obstructive hydrocephalus, Fisher scale IV. After external ventricular drainage, the magnetic resonance imaging (MRI) diagnosed a giant vertebrobasilar aneurysm (60 × 40 mm). Endovascular treatment with parent vessel occlusion was uneventful and achieved good results. The patient was extubated without deficits 2 days after, evolving on the 11th day with a convulsive state and decerebration. The MRI showed bilateral watershed cerebral ischemia, with bilateral internal carotid artery (ICA) vasospasm. Percutaneous transluminal angioplasty (PTA) was rapidly performed using a 3 × 10 mm HyperGlide™ (Medtronic, Minneapolis, MN, USA) balloon (Figure 1).

Figure 1.

A 3-year-old boy presented with vomiting evolving to coma; the CT scan (a) shows hemorrhage and a posterior fossa mass, while digital angiography (b) shows a giant vertebrobasilar aneurysm junction (c); the parent vessel occlusion with coils (d) achieves excellent clinical result; however, after clinical worsening 11 days after bleeding, an MRI evidences bilateral cerebral ischemia (e) due to carotid arteries vasospasm (f); endovascular treatment with balloon angioplasty (g) improves the arterial diameter (h), and the 1-year follow-up CT (i) shows good brain recovery. CT: computed tomography; MRI: magnetic resonance imaging.

Case 2

A 4-year-old boy presented sudden headache, drowsiness, and right hemiparesis, GCS 3, Hunt-Hess scale grade V, WFNS scale grade V. The computed tomography (CT) scan showed SAH, intraventricular, and left temporal intraparenchymal hemorrhage, Fisher scale IV. 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 etiological investigation ruled out infectious aneurysm. On the seventh day, he presented aphasia and right hemiplegia, and a CT scan ruled out rebleeding and hydrocephalus. The MRI showed diffusion restriction in the left cerebral hemisphere and severe vasospasm. An eventful PTA using a 4 × 20 mm balloon (HyperGlide™, Medtronic, USA) was performed in proximal vessels (Figure 2).

Figure 2.

A 5-year-old boy presented with sudden headache and vomiting; CT scan (a) shows temporal hematoma with ventricular hemorrhage; digital angiography (b,c) shows a distal 2 mm aneurysm in the left posterior cerebral artery (arrows), which was occluded with coils (d); MRI shows cerebral ischemia 7 days after bleeding (e) due to symptomatic left carotid artery vasospasm (f); endovascular treatment with balloon angioplasty (g) achieves good result (h); and the 6-month follow-up CT (i) shows left cerebral hemisphere atrophy. CT: computed tomography; MRI: magnetic resonance imaging.

Results

The balloon PTA improved the arterial diameter in both cases. In case 1, the patient was discharged on the 21st day with mild cognitive impairment and ataxia, modified Rankin Scale (mRS) 2. Progressive recovery occurred during a 1-year outpatient follow up, and the late MRI showed mass reduction. In the case 2, after tracheostomy and gastrostomy, the patient was discharged aphasic and hemiplegic on the 33rd day, mRS 2. After 18 months of rehabilitation, he had mild aphasia, hemiparesis, and could walk independently. The follow-up CT scan showed gliosis in the ischemic area.

Discussion

Aneurysmal SAH is rare in childhood, and the reported incidence of associated DCI in children is around 25% to 53%.^2,5–7 DCI is defined as a delayed advent of neurological deficit, decreasing of two or more points in GCS, and/or cerebral infarction unrelated to other causes (hydrocephalus, cerebral edema, metabolic disorders, or treatment of the aneurysm). ⁶ The term symptomatic vasospasm indicates the delayed neurological deficit associated with a reduction in arterial diameter. ⁶ In contrast, DCI can be asymptomatic and occur in the presence or absence of angiographic vasospasm. ⁶

The pathophysiology of vasospasm involves several mechanisms and is not completely understood. The proliferation of smooth muscle and myofibroblast can cause persistent constriction of medial smooth. ⁸ Intimal hyperplasia, deposition of collagen fibers in the vessel wall and fibrosis after SAH were also described. ⁹ The presence of hemoglobin may consume nitric oxide and activate an inflammatory response, releasing interleukin-1, an endogenous vasodilator cytokine. ¹⁰ In addition, the intraluminal platelet aggregation forming microthrombus can also occlude the arteries directly, or even produce distal embolization. ⁸ The resulting stenosis or occlusion decrease the cerebral blood flow, leading to tissue ischemia and cerebral infarction.^4,8,10

The diagnosis of cerebral vasospasm is confirmed when a reduction of < 50% in the arterial caliber is shown by CT-angiography, MR-angiography, digital subtraction angiography, or transcranial Doppler. ¹⁰ The transcranial Doppler (TCD) monitoring helps to detect vasospasm, especially in sedated or unconscious patients, and a recent consensus stated some recommendations for its use in critically ill children in the pediatric intensive care unit.¹¹ The CT perfusion and MR perfusion studies with arterial spin labeling after SAH can also detect global or regional perfusion decrease, the later exempting the use of contrast agent.^10,11

When clinical vasospasm is suspected, the initial step is usually medical treatment, using intravenous fluids, albumin, vasopressors, and inotropic agents. ⁸ Several substances have been tested to reduce the vasospasm, such as nimodipine, magnesium sulfate, statin, papaverine, nicardipine, verapamil, fasudil, amantadine, and milrinone.^4,8,12,13 The management targets maintenance of normothermia, electrolytes, and metabolic balance. ⁴ The traditional triple-H therapy, including hypervolemia, hypertension, and hemodilution has been replaced by euvolemia and induced hypertension. ¹⁰ Even without medical treatment, DCI usually has better outcomes in children than adults, probably due to collateral circulation and higher cerebral blood flow. ¹⁰ Because of the lack of specific guidelines for managing DCI in children, physicians often adapt adult treatment guidelines to pediatric patients.^1,7 However, pediatric features are distinct from adults: a study with 12 children concluded that oral nimodipine in children did not eliminate vasospasm, rebleeding, or infarction but produced significant hypotension. ² In contrast, another small pediatric series found that although nimodipine cannot reduce the incidence of vasospasm after SAH in children, it may improve the brain function without significant safety problems. ¹⁴ Therefore, prophylactic therapy using oral nimodipine (0.5–1 mg/kg every 4 hour) can be indicated in children not only to empirically reduce the risk of vasospasm, but also to improve short-term brain function, and can be discontinued or associated with vasoactive drug in case of arterial hypotension.^4,8,10 The continuous intravenous or intra-arterial infusion of milrinone, a selective phosphodiesterase 3 inhibitor, seems to be a promising option to improve confirmed vasospasm: in a study of eighty patients with SAH, 14 patients with vasospasm were treated with continuous intravenous infusion of milrinone, achieving success in 13 of them. ⁴

The refractory symptomatic vasospasm is usually treated by endovascular therapy, such as intra-arterial infusion of vasodilators and PTA,^5,8 with few reported pediatric cases of vasospasm using intra-arterial infusion of nicardipine, milrinone, and verapamil, obtaining variable results.^1,3–5,15 Chemical angioplasty with drug infusion has the advantage of acting in distal vasculature, although it has a time-limited effect and can cause hypotension resulting in cerebral hypoperfusion, or even increase the intracranial pressure due to cerebral vasodilation. ¹⁰ In contrast, the balloon PTA has long-lasting effect but is restricted for large vessels. Therefore, severe cases of diffuse vasospasm usually are initially treated with chemical angioplasty and followed by mechanical angioplasty in the same procedure, in a combination of both techniques. ⁸

Although there is a paucity of randomized controlled trials in children, some published cases demonstrated the efficacy and safety of balloon PTA to recover neurological deficits and prevent further ischemic insults.^1,7,8 In adults, 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. ¹⁶ Although the ideal timing for intervention remains unclear, treatment should 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. ¹⁷

In contrast to pharmacological treatment, restenosis of previously dilated cerebral arteries with balloon PTA has not been reported. ⁹ That durable effect is believed to be related to definitive disruption of vessel wall architecture, mainly affecting the collagen fibers and the medial layer components.^8,9 Although strong radial force and balloon diameter accuracy are critical features for treating atherosclerotic lesions, intracranial vasospasm requires slow inflation under lower pressure, ¹⁸ Indeed, PTA of vasospasm affecting cerebral arteries usually requires much lower inflation pressures than atherosclerotic arteries. ⁹ Ideally, the neurovascular balloons should be compliant, flexible, less traumatic, and have a small profile. ⁸ Those characteristics improve vessel navigation and decrease the risk of vessel rupture. Although most current devices were designed for balloon test occlusion and balloon-assisted aneurysm coiling, they can be safely used to dilate stenosis in the cerebral arteries and improve perfusion. It is recommended to inflate the balloon using a 50:50 contrast-saline solution to enable safe visualization. As they tend to have a relatively large maximum inflation diameter, these balloons must be carefully observed during inflation using radioscopy, 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.

The overall complication rate of balloon PTA is approximately 5%, and it includes vessel perforation, arterial rupture (eventually fatal), thrombosis, embolism, reperfusion injury, and displacement of surgical clips.^8,13 Even in adults, balloon PTA is often limited to proximal vessels bigger than 2 to 3 mm. ⁸ 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. ¹⁹ Nevertheless, MCA reaches almost its total diameter at the 6 months of life, while ICA and ACA approximately have an adult diameter by the age of 4 years. ¹⁹ Therefore, additional caution must be taken to perform PTA for children younger than 4 years old. Most literature regarding PTA for pediatric vasospasm is case reports of older patients, usually adolescents.^1,15 For infants and young children, however, data is scarce. The small lumen diameter and vessel fragility increase the risk of arterial injury or rupture, as well as the area of vasospasm can also preclude the use of most guiding catheters and transluminal devices.^3,5 In that situation, a mechanical angioplasty can be performed using mechanical dilatation with the microcatheter and a microguidewire. ⁵

Although the potential limit for intervention in infants related to small arterial size and devices stiffness, the improvement of the devices can overcome these obstacles and turn possible balloon angioplasty, even for babies. ¹⁰

The present study has all the limitations of a single-center retrospective study, and evaluating only two children precludes definitive statements. The absence of TCD in our hospital causing a delayed diagnosis, exceeding the 2-hour window, may have worsened the clinical outcomes. Therefore, the clinical result of PTA may have been limited, although good recovery has been observed. In addition, no objective pre- and postoperative perfusion studies were performed.

Conclusion

The therapeutic improvement over the past decades reduced the mortality from aneurysmal SAH. ¹² However, the DCI is still difficult to avoid, detect, and treat, especially in children. Therefore, management in a dedicated pediatric critical care unit with neuro focus and an aggressive neuromonitoring is recommended for early diagnosis and therapeutics of DCI. Balloon PTA may contribute to improve the 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.