Hemorrhagic Moyamoya Disease in Children
Clinical, Angiographic features, and Long-Term Surgical Outcome
Background and Purpose—Here, we describe the clinical, angiographic characteristics, and long-term surgical outcome of hemorrhagic moyamoya disease in children.
Methods—We retrospectively collected 374 consecutive children with moyamoya disease (hemorrhagic 30 and ischemic 344) between 2004 and 2012 in our hospital. The clinical and radiological characteristics of the hemorrhagic patients were retrospectively described and analyzed. All the hemorrhagic patients underwent encephalo-duro-arterio-synangiosis procedure. Digital subtraction angiography was performed to evaluate the efficacy of vascularization. Clinical follow-up outcomes were obtained through clinical visits, telephone, or letter interview.
Results—In our study, the ratio of female to male patients in the hemorrhagic group was significantly higher than the ischemic group (2:1 versus 0.9:1; P<0.05). The most frequent hemorrhagic location was intraventricular hemorrhage (n=22, 73%). In addition, significantly greater dilatation of the anterior choroidal artery and the posterior communicating artery were seen in the hemorrhagic group (P<0.05). Good or fair vascularization were observed in all the 15 children with digital subtraction angiography follow-up. Clinical outcomes showed that 25 of 30 (83%) patients had no disability (modified Rankin scale score, 0 and 1); 1 patient (3.3%) died of recurrent hemorrhagic stroke.
Conclusions—The presence of anterior choroidal artery and posterior communicating artery dilation may be associated with the bleeding episode in the children with hemorrhagic moyamoya disease. The encephalo-duro-arterio-synangiosis surgery can effectively increase the cerebral blood flow in children, which may decrease the incidence of recurrent hemorrhage.
Moyamoya disease (MMD) is a chronic cerebrovascular disorder defined by progressive stenosis or occlusion of the intracranial vessels. Because these arteries gradually stenose, a collateral network of capillaries develops at the base of the brain, producing the characteristic reticulate appearance (puff of smoke) on angiography.1,2 Although hemorrhage is one of the major symptoms in adult, it is uncommon in pediatric patients, ranging from 0% to 9.3%.3,4 Given the low incidence, the clinical characteristics and surgical outcome of pediatric hemorrhagic MMD has not been systematically described.
In this retrospective study, a consecutive series of 30 pediatric patients with hemorrhagic MMD was described. The clinical, angiographic differences and the long-term surgical outcome between the hemorrhagic and ischemic pediatric MMD patients were evaluated.
Materials and Methods
Consecutive patients <17 years of age with MMD receiving treatment in our hospital were included. Diagnosis of all the patients was according to the current diagnostic criteria.5 Children with unilateral MMD or the presence of secondary moyamoya phenomenon caused by meningitis, Down syndrome, systemic vasculitis, hyperthyroidism, neurofibromatosis, leptospiral infection, or previous skull-base radiation therapy were not included in our study series.
Hemorrhage was diagnosed with the use of computed tomography, cerebral infarction was with magnetic resonance imaging, and all of the patients underwent magnetic resonance angiography and digital subtraction angiography to confirm the diagnosis. Children with intracranial hemorrhage were classified as hemorrhage group, whereas children with transient ischemic attacks, cerebral infarction, headaches, or seizures were classified as ischemia group. The anterior choroidal artery (AChA) and the posterior communicating artery (PComA) were graded according to the previously published methods.6,7
With regard to the AChA, normal without dilation was defined as grade 0; dilation of the AChA within the choroidal fissure as grade 1; dilation and extension of the AChA beyond the choroidal fissure as grade 2; disappearance of the AChA because of the occlusion of ICA as grade 3. As to the PComA, negative without dilation was defined as grade 0; dilation of the PComA without abnormally extensive branches as grade 1; dilation of the PComA with abnormally extensive branches as grade 2; and disappearance of the PComA because of the occlusion of ICA as grade 3.
Treatment Option and Clinical Follow-Up
All the patients in the hemorrhage group underwent encephalo-duro-arterio-synangiosis (EDAS) procedure by 1 neurosurgeon in our department. Recurrent intracranial hemorrhage and ischemic events were confirmed using computed tomography and magnetic resonance imaging. Neurological outcome was assessed using modified Rankin scale. The development of collateral circulation through the EDAS was assessed by digital subtraction angiography according to the system that was described by Matsushima et al,8 where good indicates that the postsurgical collateral vessels achieved vascularization of two thirds of the middle cerebral artery distribution, fair indicates that the postsurgical collateral vessels achieved vascularization of one third to two thirds of the middle cerebral artery distribution, and poor indicates that the postsurgical collateral vessels achieved little or no vascularization.
Data comparison was evaluated using the χ2 test, Fisher exact test, Mann–Whitney U test, and t test (SPSS 19.0, statistical significance was set at P<0.05).
Thirty children (12.6±3.1 years; range, 4–16 years) were presented with hemorrhagic symptoms and 344 children (9.4±3.8 years; range, 2–16 years) were manifested with ischemic symptoms (P<0.05). The ratio of female to male patients in the hemorrhage group was significantly higher than the ischemia group (2:1 versus 0.9:1; P<0.05).
Among the 30 hemorrhagic children, 24 (80%) of the patients were asymptomatic before the onset of their first bleeding episode, whereas 6 (20%) of the patients showed headaches or minor transient ischemic attack before hemorrhage.
In the ischemic cohort, transient ischemic attack was the most common initial symptom (230, 67%). The others were infarction (80, 23%), headache (27, 7.8%), and seizure (7, 2.0%).
In addition, the most frequent hemorrhagic location was intraventricular hemorrhage (n=22, 73%), followed by intracerebral hemorrhage (n=6, 20%), and subarachnoid hemorrhage (n=2, 6.7%).
The proportion with abnormal dilation of AChA was obviously higher in the hemorrhage group than in the ischemia group (82% versus 30%; P<0.05; Figure 1). In addition, the proportion with abnormal dilation of PComA was also higher in the hemorrhage group than in the ischemia group (87% versus 46%; P<0.05; Tables 1 and 2).
Surgical Treatment and Follow-Up Angiographic Findings
All the patients underwent bilateral revascularization surgery. Fifteen (15/30, 50%) patients had underwent digital subtraction angiography in the follow-up (mean interval, 6.5±1.1 months; range, 5–9 months). The postoperative digital subtraction angiography results showed that good collateral circulation in 12 patients and fair collateral circulation in 3 patients (Figure 2). In addition, moyamoya vessels were decreased in 11 patients (73%) and were unchanged in 4 patients (27%).
Follow-Up Surgical Outcome
Over a mean follow-up of 6.4±2.2 years (range, 3–11 years), only 1 patient (3.3%) had an episode of recurrent intracranial hemorrhage 4 years after the surgery and died. Six children complained of ischemic symptoms such as intermittent headache and limb weakness, and the other children did not complain of any discomfort. Of the 29 surviving patients, 25 (83%) had no disability (modified Rankin scale score, 0 and 1), 3 (10%) had mild or moderate disability (modified Rankin scale score, 2 or 3), and only 1 (3.3%) had unfavorable outcome because of the initial hemorrhage (modified Rankin scale score, 4).
Most of the studies about the pediatric hemorrhagic MMD were case reports. An incidence rate of 3% has been reported in Korea, which was low compared with the adults (range, 25%–60%).3,9,10 In our study, the incidence of pediatric hemorrhagic MMD was 8.02%. Furthermore, the ratio of female to male patients in hemorrhagic MMD was 2:1, which was similar to the previous reports.3,11 The results suggest there is a female dominance in sex distribution of hemorrhagic MMD in children.
In this study, the proportions of abnormal dilation of AChA and PComA in the children with hemorrhagic MMD were associated with significantly higher values than the children with ischemic MMD. A previous study on 107 patients with hemorrhagic MMD also exhibited this phenomenon.6 In our cohort, although the dilation proportion of AChA in hemorrhagic children was similar to that in patients (<20 years old) in the previous study (82% versus 80%), the proportion with dilation of the PComA was much higher (87% versus 20%).6 The normal AChA and PComA are reported to provide blood to areas near the lateral ventricle under normal conditions. However, in patients with MMD, these normal branches convert into collateral vessels and their function as collateral vessels results in increase of blood flow. The exceedingly dilated and fragile branches of the AChA or PComA may rupture and produce hematomas in intraventricular hemorrhage.7 We speculated that the high dilation proportion of AChA and PComA may lead to the high proportion of intraventricular hemorrhage in our study.
Because of the limited number of reports and sample sizes, the natural course of the rebleeding rate and the optimal treatment in pediatric patients with hemorrhagic MMD remains unclear. Some reports showed great benefit in decreasing the incidence of rebleeding after indirect revascularization.3,11 In 2013, Liu et al11 reported on 13 children (aged <18 years) with hemorrhagic MMD who received indirect bypass and conservative treatment. No children in the surgery group suffered rebleeding, whereas 3 children had recurrent hemorrhage during the conservative observation period. In 2012, Ahn et al3 described a series of 13 children (aged <18 years) with hemorrhagic MMD who received indirect bypass surgery after neurological stabilization, and only 1 patient suffered rebleeding (7.7%). In our case series, among all the children underwent EDAS revascularization during the follow-up, only 1 child had recurrent intracranial hemorrhage (3.3%). Most of the children with hemorrhagic stroke had a good prognosis after revascularization. Hence, this study results demonstrate that EDAS may be a good choice for pediatric patients with hemorrhagic MMD and effective revascularization is useful to decrease the incidence of neurological deterioration in a majority of patients.
Our study had some limitations. First, all the patients in this study were enrolled from a single neurosurgery center, potential selection bias may occur. Second, the sample remains small for further analysis.
The presence of AChA and PComA dilation may be associated with the bleeding episode in the children with hemorrhagic MMD. The EDAS surgery can effectively increase the cerebral blood flow in children, which may decrease the incidence of recurrent hemorrhage.
We thank all the patients and healthcare providers who participated in this study.
Sources of Funding
This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81171083) and the Commission of Beijing Municipal Science and Technology, municipal clinical special application study, special fund project (No. Z14110000211441).
- Received June 19, 2015.
- Revision received October 7, 2015.
- Accepted October 8, 2015.
- © 2015 American Heart Association, Inc.
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