Introduction

Moyamoya disease is characterized by gradual stenosis or occlusion of the bilateral internal carotid arteries. This occlusion induces the development of collateral circulation called Moyamoya vessels in the basal ganglia.29)43) This disease is more frequent among young teenagers and those in their 30s and 40s, and represents the most common cause of ischemic stroke in children.7) Moyamoya disease is generally characterized by cerebral ischemia and cerebral infarction in children, and by hemorrhagic lesions in adults. Various symptoms such as aphasia and hemiparesis may appear, depending on the sites of cerebral ischemia or hemorrhage.10)29)

Medical treatment is ineffective for Moyamoya disease,29) but there are three representative surgical treatment techniques.25) The first is a direct anastomosis such as a superficial temporal artery-middle cerebral artery (STA-MCA)2)6)8) procedure. The second is an indirect anastomosis such as encephaloduroarteriosynangiosis (EDAS),34) encephalomyosynangiosis (EMS),23) encephaloduro-arteriomyosynangiosis (EDAMS),27) encephalogaleosy-nangiosis (EGS),18) bifrontal encephalogaleoperiosteal synangiosis (BEGPS),40) and multiple burrhole surgery.24) The third is a combined bypass surgery.20) The goal of these surgical treatments is to minimize and prevent the symptoms of cerebral ischemia by effectively forming collateral circulation from the outside to the inside of the cranial cavity.25)

Of the three surgical techniques, indirect bypass does not produce immediate effects. Collateral circulation develops 3?4 months after surgery,14)15)45) creating a risk for pre- and post-surgery ischemic stroke.19)41) Nevertheless, indirect bypass is widely-used because the anastomosis is technically simple and has fewer complications than direct bypass.39)

We presently identified the effectiveness of indirect bypass as a treatment for Moyamoya disease by analyzing the clinical and cerebral angiographic results. Additionally, clinical factors and surgical techniques favoring efficient collateral circulation were identified.

Materials and Methods

Forty-five patients (66 hemispheres) with confirmed or probable Moyamoya disease or probable Moyamoya disease underwent indirect bypass surgery at Soonchunhyang University hospital between May 2002 and May 2009. Twenty-eight 28 patients (42 hemispheres) were followed by cerebral angiography for at least 6 months. Those who underwent direct bypass were excluded. Among the subjects, eight patients (13 hemispheres) were male and 20 patients (29 hemispheres) were female. Their ages at the time of diagnosis ranged from 2-62 years, with a mean of 23.9± 17.1 years. The follow-up periods ranged from 6?67 months, with a mean of 23±18.6 months.

The subjects were operated on under general anesthesia. During the surgery, the patients were continuously monitored to maintain normal carbon dioxide tension (PCO2), blood pressure, and body temperature. Urine output was measured, and appropriate fluids were supplied to prevent dehydration.

For EDAMS, the superficial temporal artery (STA) was located in advance using ultrasonography, and the skin was incised beginning 1 cm above the root of zygoma of the temporal bone and continuing along the STA, while sufficiently preserving the surrounding soft tissues, and curving toward the back from the intersection with the linea temporalis. After detaching the temporal muscle, an incision 5-6 cm in length and 6-7 cm in width was made in the skull. The dura was incised, while preserving the main branch of the middle meningeal artery, and the dura was pushed inside between the dura and the arachnoid membrane so that the periosteal layer of the incised dura mater would contact the surface of the arachnoid membrane. The middle meningeal artery branch was reversed and sutured to the arachnoid membrane. The arachnoid membrane was opened at many sites and the STA was sutured to the pia mater using 10-0 nylon sutures. Then, the temporalis muscle was sutured to a dural edge, and the inner table of the bone flap was removed to reduce the mass effect. If the mass effect was a concern due to the thickness of the temporalis muscle, the muscle layer was divided into two halves, and only the inner half was transplanted to the pia mater, with its edge sutured to the dura. 

For the BEGPS technique, the scalp was incised in the shape of a yin-and-yang symbol in front of the coronal suture, and a 4 x 4 cm incision was made in the skull around the midline. Then, the galea was turned over and inserted along the midline falx.

Cerebral angiography was conducted for a minimum of 6 months after surgery to evaluate the development of collateral circulation. As previously defined,31) a good score (group A) represented revascularization of more than two-thirds of the MCA distribution through the external carotid artery (ECA), a fair score (group B) represented revascularization of one- to two-thirds of the MCA distribution, and a poor score (group C) represented slight or no revascularization (Fig. 1).

A t-test was used to analyze the development of collateral circulation according to gender, surgical technique, and age at the time of discovery. The correlation between the clinical manifestation and the development of collateral circulation determined by the Suzuki classification method was analyzed with a Z-test.

The development of collateral circulation in the anterior cerebral artery (ACA) for BEGPS was classified as good, fair, or poor,31) depicted in Fig. 2. Patients whose collateral circulation was two-thirds or more of the ACA distribution were grouped as good; those with collateral circulation of between one- and two-thirds were grouped as fair; and those showing weak or no collateral circulation were grouped as poor.

Results

The child and adult patients contributed 19 and 23 hemispheres, respectively. Of the 29 patients with Moyamoya disease, 13 were males and 29 were females. Cerebral infarction was the most frequent clinical manifestation, followed by cerebral hemorrhage, transient cerebral ischemia (TIA), and seizure. Preoperative cerebral angiography was classified into stages 0 to 6 according to Suzuki et al.43 Stage 3 was the most frequent stage, followed by stage 4, stage 2, stage 1, and stage 5 (Table 1).

Among the children, group A, B, and C consisted of 12 cases (63.2%), six cases (31.6%), and one case (5.2%), respectively. Among the adults, group A, B, and C consisted of seven cases (30.5%), 11 cases (47.8%), and five cases (21.7%), respectively. Postoperative development of collateral circulation was better in the children (P = 0.0344; Table 2). [Authors: The reason the above paragraph was re-done is that you had presented results both here and in the table. It really should be one or the other. The remaining paragraphs were not edited as much.]

Based on the postoperative cerebral angiography results in males, group A comprised five cases (38.5%); group B, five cases (38.5%); and group C, three cases (23.0%). For females, group A consisted of 14 cases (48.3%); group B, 12 cases (41.4%); and group C, three cases (10.3%). Females tended to show slightly better postoperative development of collateral circulation, but the difference was not statistically significant (P = 0.5659; Table 3).

Using the postoperative cerebral angiography results for the nine patients with cerebral hemorrhage, one case (11.1%) was classified into group A, five cases (55.6%) were in group B, and three (33.3%) were in group C. Of the 27 cases with cerebral infarction, 15 (55.6%) were in group A, nine (33.3%) in group B, and three (11.1%) in group C. There were only three TIA cases: two (66.7%) were in group A and one (33.3%) was in group B. The development of collateral circulation tended to be better in patients with cerebral infarction and TIA compared with cerebral hemorrhage, but not significantly so (P = 0.1087; Table 4).

Considering the postoperative cerebral angiography by surgical technique, 18 (46.2%) of the 39 patients who received EDAMS were classified into group A, 15 cases (38.5%) into group B, and six cases (15.3%), into group C. For the three patients who received EDAS, group A consisted of one case (33.3%), and group B consisted of two cases (66.7%). Compared with EDAS, EDAMS tended to give better postoperative development of collateral circulation, but the difference was not significant (P = 0.6764; Table 5).

The postoperative cerebral angiography results were also classified according to preoperative Suzuki stage. For preoperative stage 1 patients, group A consisted of two cases (66.7%) and group B consisted of one case (33.3%). For stage 2, group A comprised four cases (40.0%), group B comprised five cases (50.0%), and group C comprised one case (10.0%). For stage 3, group A consisted of eight cases (53.3%), group B comprised four cases (26.7%), and group C comprised three cases (20.0%). For stage 4, group A included five cases (38.5%), group B included six cases (46.2%), and group C included two cases (15.3%). No significant differences in post-operative development of collateral circulation were observed based on pre-operative Suzuki stage (P = 0.7399; Table 6).

BEGPS, also called ribbon surgery, was performed in 21 cases, to promote collateral circulation in the bilateral anterior cerebral arteries. Three cases (14.3%) showed good results, with collateral circulation from the ECA branch distributed in two-thirds or more of the total anterior cerebral artery area. The results were fair in 12 cases (57.1%), in which collateral circulation was distributed in one- to two-thirds of the total anterior cerebral artery area. In six cases (28.6%), collateral circulation was distributed in one-third or less of the total anterior cerebral artery area, which was considered a poor result (Table 7).

Discussion

Many surgical techniques have been developed for treatment of Moyamoya disease4). These can be classified generally into direct bypass and indirect bypass. The many different types of indirect bypass include EDAS, EMS, EDAMS, EGS, BEGPS, and multiple burr hole surgery.7)9)10)18)19)21)23-25)27)34)40)42)44) Vascular structures used for these surgeries include the STA, dura, temporalis muscle, and galea. Indirect bypass, which generates spontaneous angiogenesis between vascular structures donated from the brain surface, is widely-used because of its technical simplicity.39) However, it has a disadvantage in that collateral circulation is formed 3-4 months after surgery.14)15)45) Furthermore, indirect bypass presents a risk for pre- or post-surgery ischemic stroke before or after surgery, making appropriate anesthesiological management vital for preventing stroke.19)22)26)41) Post-operative development of collateral circulation depends on the size of the craniotomy and the area of the indirect anastomosis, so surgical design is a critical factor.28)32)

During general anesthesia, we maintained PaCO2 in the arterial blood at 35-40 mmHg and the mean arterial pressure at 75 mmHg or higher, and were careful not to decrease the PaCO2 or the mean arterial pressure. We also guarded against dehydration and an increase in body temperature after surgery, and considered pain management after surgery to prevent hyperventilation attributable to pain. When post-operative hyperventilation occurred, an oxygen tent was used to prevent cerebral ischemia by cerebrovascular spasm, which can occur with decreased PaCO2 in arterial blood.

Young patients with Moyamoya disease presently experienced very good development of collateral circulation following indirect anastomosis, but collateral circulation was generated in only 40?50% of adult patients. Therefore, direct bypass is preferred and given priority as a surgical treatment in adult patients with Moyamoya disease.13)36) Nevertheless, according to a recent report,16) indirect bypass is still the most frequently used surgical technique for treating Moyamoya disease in Japan. The same authors reported that TIA symptoms disappear within 1 year in patients who undergo EDAS.31) Furthermore, there have been many reports that collateral circulation is generated in one-third or more of the MCA area in 62-84% of patients who undergo only EDAS.1)17)30)31)33)46) In contrast, two studies have reported that collateral circulation did not develop in some patients after indirect bypass.35)37)

In one study, EDAMS achieved better postoperative cerebral angiography results than EDAS, regardless of the STA-MCA bypass performance.25) This agrees with the results of the present study. However, because only three cases underwent EDAS in our study, the result has no statistical significance. The operation field of EDAS surgery is along the course of the parietal branch of the STA, which is commonly used as a donated vascular structure, and this limits the extent of the craniotomy. EDAMS allows a greater surgical field and wider extent for the craniotomy, which may account for the better development of collateral circulation with EDAMS compared with EDAS.

Many EDAMS surgical techniques have been reported, 25)39) and many disagreements remain, particularly about opening the arachnoid membrane. Kim et al.25) incised only the dura, while maintaining an intact arachnoid membrane. Ozgur et al.39) incised the arachnoid membrane at many points along the sulci. The former is simple, but its disadvantage is that the temporalis muscle, STA, and galea may not directly contact the pia mater. The latter is associated with the danger of hemorrhage when opening the arachnoid membrane, as well as a risk for leakage of cerebrospinal fluid and the resulting pseudomeningoceles or subdural hygroma. However, the advantage is easier angiogenesis due to reduced dead space. The present study used the latter technique. The arachnoid membrane was opened at several points to maximize angiogenesis where the STA, dural edge, and temporalis muscle contact the brain surface. After surgery, 85.7% of our cases showed angiogenesis in one-third or more of the MCA, which is a higher rate than the 40-50% reported in other studies.29) For example, collateral circulation developed from the perforated site after extraventricular drainage in a patient with intraventricular hemorrhage. Thus, opening the arachnoid membrane seems to be more effective for achieving collateral circulation.

Some believe that direct bypass is better for treating Moyamoya disease, but the evidence is still insufficient.42) According to Ishikawa et al.19), there was no difference in the clinical result between direct and indirect bypass based on a long-term follow-up of the development of collateral circulation. Although direct bypass provided better blood flow results immediately after surgery, it did not result in long-term blood flow to the MCA. The authors stated that the cause was a gradual occlusion of the recipient artery owing to the progression of Moyamoya disease.3)37)

A direct bypass is technically more difficult than an indirect bypass and requires close attention and experience. Direct bypass offers a high likelihood of failure for recipient arteries 1 mm or smaller in diameter, due to the difficulty of the arteriotomy, and is difficult to perform in patients with medical problems, because operative time increases owing to vascular occlusion or hemodiapedesis after the anastomosis.12)42) Furthermore, TIA and ischemic stroke after a direct bypass have been reported in some cases. An indirect bypass has fewer post-operative complications and is safer than a direct bypass.11)38)42)

Marcus et al.46) reported on the post-operative development of collateral circulation according to age. Indirect bypass achieved better results in children, whereas direct bypass was better in adults, although indirect bypass also showed good collateral circulation in adults. The authors improved on the technique by using combined revascularization. Children also showed better results in our study: 94.8% of children and 78.3% of adults showed development of collateral circulation in one-third or more of the MCA (P=0.0344).

Many recent studies have reported good results using combined revascularization, rather than a single direct or indirect bypass operation.5)20)26)29)42) However, the present study investigated only patients who underwent indirect bypass and did not compare differences in cerebral angiography or clinical results between direct bypass and combined revascularization cases. In the future, we will compare the clinical results and degree of collateral circulation on cerebral angiography based on a long-term follow-up of patients treated with direct bypass or combined revascularization.

Conclusion

Approximately 86% of the patients with Moyamoya disease developed collateral circulation in one-third or more of the MCA after indirect bypass surgery. The results were much better in children aged ≤15 years, although adults also experienced a good degree of collateral circulation. In terms of the development of collateral circulation, EDAMS was better than EDAS. It appears that in addition to the contact of the dura with the brain surface, the opening of the arachnoid membrane at several points accelerated collateral circulation development. Although the development of collateral circulation may require several months after surgery, indirect bypass generated sufficient collateral circulation in patients for whom direct bypass would have been difficult. Therefore, indirect bypass is believed to be a good treatment technique for Moyamoya disease, with better results expected with BEGPS.

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