Advances and Surgical Considerations in the Treatment of Moyamoya Disease

Arias, Eric J. MD*; Derdeyn, Colin P. MD*,‡,§,¶; Dacey, Ralph G. Jr MD*,¶; Zipfel, Gregory J. MD*,‡,¶

Section Editor(s): Bendok, Bernard R. MD; Levy, Elad I. MD

doi: 10.1227/NEU.0000000000000229
Extracranial and Intracranial Occlusive Disease

Moyamoya is a rare disorder that involves steno-occlusive arterial changes of the anterior circulation, along with proliferative development of basal arterial collaterals. It is either idiopathic (called moyamoya disease) or the result of a specific underlying condition such as atherosclerosis, radiation therapy, or sickle cell disease (called moyamoya syndrome or phenomenon). In recent years, numerous insights into and advances in the understanding, evaluation, and management of moyamoya patients have occurred. This article briefly reviews the spectrum of moyamoya conditions and then provides a synopsis of numerous recent investigations that shed light on various aspects of the disease, including its clinical characteristics, natural history, underlying pathology, imaging, surgical techniques, and long-term patient outcome.

ABBREVIATIONS: CBF, cerebral blood flow

EDAS, encephaloduroarteriosynangiosis

MCA, middle cerebral artery

MMD, moyamoya disease

STA, superficial temporal artery

TIA, transient ischemic attack

Departments of *Neurological Surgery,

Neurology, and

§Radiology and

Stroke and Cerebrovascular Center, Washington University School of Medicine, St. Louis, Missouri

Correspondence: Gregory J. Zipfel, MD, Department of Neurological Surgery, Campus Box 8057, 660 S Euclid Ave, St. Louis, MO 63110. E-mail:

Received September 10, 2013

Accepted October 11, 2013

Article Outline

Moyamoya disease (MMD) is an idiopathic cerebrovascular disorder characterized by stenosis or occlusion of the supraclinoid internal carotid arteries with subsequent hypertrophy and proliferation of lenticulostriate arteries to form a collateral network. The name stems from the appearance of these collaterals on conventional catheter angiography; moyamoya translated from Japanese means a hazy cloud like a puff of cigarette smoke.1 Moyamoya syndrome or phenomenon refers to a similar condition that occurs when an underlying cause such as atherosclerosis, radiation therapy, or sickle cell disease produces unilateral or bilateral steno-occlusive arterial changes and associated moyamoya collaterals. Patients with MMD and moyamoya phenomenon may present with either hemorrhagic or ischemic stroke. There is no proven medical treatment for the prevention of stroke in this population. Surgical revascularization is often pursued to improve cerebral blood flow (CBF) and to prevent future ischemic stroke. The role of revascularization for the prevention of hemorrhagic stroke is less clear. A variety of direct and indirect bypass techniques have been developed. Recent investigations have shed light on many important aspects of this poorly understood, idiopathic condition. These include phenotypic differences between Asian and North American/European moyamoya, natural history, moyamoya pathology, the role of imaging, and techniques to improve surgical interventions and outcomes. This article reviews these recent data, with special emphasis on results from studies examining the North American/European phenotype.

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MMD was originally described in Asia. One of the first and largest reports of the disease encompassed 100 patients seen in Japan between 1961 and 1980.2 Of these, 46 were children <15 years of age and 54 were adults, revealing a bimodal age distribution with 1 peak occurring in the first decade and a second peak in the fourth decade. A minor sex disparity was noted, with 60 females and 40 males making up the 100 patients (female:male ratio, 1.5:1). Other reports have demonstrated that the presenting symptomatology varies depending on patient age. Children present most commonly with ischemic symptoms (79%),3 which include repetitive transient ischemic attacks (TIA; 43%), TIA with infarction (40%), and infarction alone (14%).4 Adults present most commonly with intracerebral hemorrhage (42%-58%) rather than TIA or infarction (27%-32%)5,6 A very similar clinical phenotype of MMD has been described in other Asian countries, including Korea.7 According to these reports, the Asian phenotype of moyamoya is that of children (male or female) presenting primarily with cerebral ischemia and middle-aged adults (slight female predominance) presenting with intracerebral hemorrhage. The prevalence of the Asian phenotype of MMD has been reported to be as high as 3 to 6.07 per 100 000.8-10

Several recent reports have characterized MMD in North America and Europe. Data from these studies demonstrate notable differences in the clinical characteristics of North American and Asian patients.11-15 The majority of North American and European patients with moyamoya are adults in their third through fifth decades of life, and a high percentage of these patients are women (female:male ratio, nearly 3:1).13 Moreover, cerebral ischemia is the most frequent manner of presentation, with about three-fourths of North American and European adults with moyamoya presenting with ischemic symptoms.12,16,17 This is in contrast to Asian adults, who present primarily with hemorrhagic symptoms,2 although some recent data suggest that this may be shifting in Asia also.10 Other differences between the 2 phenotypes have also been identified, including a higher percentage of North American patients having unilateral steno-occlusive arterial changes with collateral formation and a higher percentage of patients with an identifiable underlying condition, including atherosclerosis,18 radiation therapy,19 sickle cell disease,20 Down syndrome,21 and neurofibromatosis type 1.22 In summary, the North American/European phenotype of moyamoya involves women in the fourth or fifth decade of life presenting with ischemic symptoms, with a higher incidence of moyamoya syndrome resulting from a specific underlying cause. The prevalence of MMD in the United States appears much lower than in Japan and other Asian countries, with a recent study estimating the prevalence in California and Washington at 0.086 per 100 000.23

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Understanding the natural history of moyamoya is a critical component of effectively managing and treating this patient population; however, 3 issues have made determining this natural history challenging. First, moyamoya is a rare condition that makes clinical evaluation of large patient cohorts difficult. Second, moyamoya has different clinical characteristics depending on patient age, geographical location, and manner of presentation, factors that reduce this already small patient cohort further. Third, very few prospective data on the natural clinical course of these patients after initial diagnosis have been published to date. Therefore, the following review of the natural history of moyamoya should be viewed with these limitations in mind.

Numerous authors have examined the natural history of untreated symptomatic MMD in the pediatric population and have found it to be unfavorable.24-26 Half of the pediatric patients who present with TIA-type symptoms continue to have these types of attacks at a mean follow-up of 7 years.27 The condition is associated with gradual, progressive neurological and cognitive deterioration.24 In a series of 27 Japanese pediatric moyamoya patients (age range, 11 months-5 years) with long-term follow-up (range, <4-15 years), 7 (26%) demonstrated mild intellectual or motor impairment, 3 (11%) required special school or care by parents or institutions after reaching the teen years, 2 (7%) needed continuous 24-hour care, and 1 (3%) died.24 Studies such as these indicate that untreated pediatric MMD likely has a poor clinical course over time.

For adult MMD, the different clinical characteristics between North American and Asian adult moyamoya phenotypes necessitate an examination and differentiation of the natural history of these 2 conditions separately. Studies examining Asian moyamoya in adults have focused primarily on recurrent hemorrhagic events. Fujii and colleagues28 performed a multicenter retrospective questionnaire study of 290 patients with hemorrhagic MMD, 138 of whom were treated conservatively. They documented a rebleed rate of 28.3% in these patients. Kobayashi and colleagues29 performed a retrospective study of 42 adult patients with hemorrhagic MMD, all of whom were treated conservatively. They reported an annual rebleed rate of 7.0% (ipsilateral, 79%; contralateral, 21%) and an annual mortality rate of 28%.

For North American adults with moyamoya, natural history studies have focused primarily on recurrent ischemic events because they are the most common presenting symptom in this population. Chiu and colleagues12 performed a retrospective analysis of 35 North American patients with angiographically proven MMD, the majority of whom presented with ischemic symptoms. Seven percent of their patient cohort was of Asian descent. They reported a crude annual rate of recurrent stroke in 10.3% of patients, with a recurrent stroke risk of 18% in the first year after diagnosis and a recurrent stroke risk of 5% per year thereafter. Hallemeier et al13 performed a retrospective analysis of 34 North American adults with moyamoya phenomenon (Figure 1). Three percent of their patient cohort was of Asian descent. They reported that in patients with unilateral moyamoya presenting with ischemic symptoms and treated medically, the 5-year risk of stroke was 65% after initial symptom onset. None of these patients developed contralateral disease during follow-up. They also reported that in patients with bilateral moyamoya presenting with ischemic symptoms and treated medically, the 5-year risk of stroke increased to 82% after initial symptom onset. Importantly, many of these patients developed symptoms referable to a previously asymptomatic hemisphere. Most recently, Gross and Du17 performed a retrospective analysis of 42 North American patients diagnosed with symptomatic MMD or moyamoya phenomenon. Ten percent of their patient cohort was of Asian descent. They reported annual rates of ischemic and hemorrhagic stroke of 13.3% and 1.7%, respectively. Statistically significant risk factors for subsequent events included female sex and stroke presentation within 3 years.17

From these studies, it appears that Asian and North American patients with symptomatic moyamoya are at significant risk of recurrent neurological events, particularly those patients with bilateral angiographic involvement. The risk appears to be highest in the first few years after presentation. Importantly, however, the vast majority of available data on the natural history of Asian and North American moyamoya are drawn from retrospective studies and therefore are subject to the inherent biases of this study design. To address this shortcoming and to begin to examine how cerebral hemodynamic assessment may affect the natural history of North American moyamoya, we initiated a National Institutes of Health--funded multicenter prospective observational study in 2009.30 Results from this trial, once available, should shed valuable light on the natural history of this particular form of moyamoya.

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It is likely that MMD represents 2 distinct processes: an obliterative vasculopathy, which may be variable in origin and involves the terminal internal carotid artery and the proximal middle and anterior cerebral arteries, and proliferation and hypertrophy of the lenticulostriate arteries.18,31 These may serve to provide some collateral flow and are certainly secondary to the occlusive disease, at least temporally. The ability to develop these moyamoya vessels is likely variable as well and probably relates to age of onset (younger) and genetic factors.32

Several lines of evidence strongly suggest that genetics likely play an important role in MMD. A 7% to 12% familial occurrence in the Japanese population has been reported.9 Other genetically inherited disorders, including Down syndrome, neurofibromatosis type 1, and collagen vascular disorders, have been linked to the incidence of MMD.9 Associations with specific HLA haplotypes and loci on chromosomes 3, 6, 8, 12, and 17 have been reported.33-36 Mutational analyses have identified RNF213 as a susceptibility gene for MMD because a founder mutation, p.R4859K, was noted in 95% of families with MMD, 73% of sporadic moyamoya cases, and only 1.4% of the general population.37 A type of X-linked familial moyamoya syndrome has been associated with Xq28 deletions of BRCC3 and MTCP1/MTCP1NB.38

An association between autoimmune diseases and moyamoya has also been reported. Type 1 diabetes mellitus is found in 8.5% of moyamoya patients compared with 0.4% in the general population. Thyroid disease is found in 17.0% of moyamoya patients and 8.0% in the general population.39 Elevated thyroid autoantibodies have also been observed in patients with MMD,40 and systemic lupus erythematosus has been associated with the development of symptomatic MMD.41

In addition to genetic and autoimmune influences, numerous molecules and growth factors have been linked to patients with MMD. Transforming growth factor-β, platelet-derived growth factor, basic fibroblast growth factor, and hepatocyte growth factor have all been identified in the cerebrospinal fluid and intracranial or temporal arteries in patients with MMD.42-44 Increased levels of vascular endothelial growth factor, matrix metalloproteinase-2, matrix metalloproteinase-9, and matrix metalloproteinase-9/NGAL have been identified in the urine of patients with MMD.45 Increased levels of matrix metalloproteinase-9 have also been found in the serum of patients with MMD.46 Whether any of these play a causal role in the pathophysiology of MMD, however, remains to be determined. Many of these factors may be expressed in response to the occlusive vasculopathy and ischemia.

Moyamoya collaterals may form secondary to a variety of steno-occlusive vasculopathies that involve the terminal internal carotid artery and its branches.31 The most common of these is atherosclerotic disease. Histological sectioning of arteries in the circle of Willis in a patient with known moyamoya phenomenon demonstrated patchy atherosclerosis with narrowed to completely occluded lumens in addition to the classically described findings of MMD, including intimal thickening, fibrosis, internal elastic lamina irregularity, and duplication.18 In addition, hypertrophy and proliferation of lenticulostriate vessels were identified.

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Digital subtraction angiography has been the gold standard in the evaluation and diagnosis of MMD from the time of its initial description. Suzuki and Takaku1 described 6 separate angiographic stages of moyamoya based on the pattern of steno-occlusion and collateral formation. Grade I refers to narrowing of the internal carotid artery apex without moyamoya collaterals. Grade II refers to internal carotid artery stenosis, along with initiation of moyamoya collaterals. Grade III refers to progression of the internal carotid artery stenosis with intensification of moyamoya collaterals. Grade IV refers to development of external carotid artery collaterals. Grade V refers to intensification of external carotid artery collaterals, along with a reduction of moyamoya collaterals. Grade VI represents the final stage of the disease process with total occlusion of the internal carotid artery and disappearance of moyamoya collaterals.1 Although the Suzuki and Takaku grading scheme is commonly used to categorize the severity of moyamoya in patients, the manner in which each grade affects the natural history and response to treatment is poorly understood.

Investigators seeking to advance the radiologic techniques by which moyamoya patients are evaluated have focused primarily on developing methods to assess cerebral hemodynamics with the hope of identifying a high-risk patient population who would most likely benefit from surgical revascularization, methods to help differentiate patients with MMD from those with moyamoya syndrome with the notion that the natural history and response to treatment of these 2 conditions may be different, and methods to guide and improve the surgical procedure itself.

Regarding cerebral hemodynamics, several techniques originally designed and applied to other steno-occlusive vasculopathies have been used in moyamoya patients. They can be categorized into 2 main groups: methods designed to identify stage I hemodynamic failure typified by autoregulatory vasodilation leading to a reduction in cerebrovascular reserve and methods designed to identify stage II hemodynamic failure typified by exhaustion of autoregulatory vasodilatory capacity and an increase in oxygen extraction fraction. For the former, paired CBF measurements before and after exposure to a vasodilatory stimulus such as intravenous acetazolamide, inhaled CO2, or breath holding are used to identify reduced cerebrovascular reserve. Common imaging techniques to perform these CBF measurements include single-photon emission computed tomography,47 xenon-enhanced computed tomography,48 arterial spin-labeling magnetic resonance (MR),49 computed tomographic perfusion,50 and transcranial Doppler.51 For the latter, positron emission tomography has been the principal method by which oxygen extraction fraction is measured (Figure 2).48 Although cerebral hemodynamic assessment has become a common component of the preoperative workup of moyamoya patients, it is important to note that the relationship between any hemodynamic compromise and the natural history and response to treatment of moyamoya patients is poorly characterized. As previously mentioned, we initiated a prospective observational study using positron emission tomography to test the hypothesis that increased oxygen extraction fraction in the cerebral hemisphere beyond the occlusive lesion is a predictor of subsequent stroke risk in medically treated patients with moyamoya phenomenon.30 Results from this trial, once available, should shed valuable light on the issue of cerebral hemodynamics and its role in the assessment of moyamoya patients.

Regarding techniques to help differentiate moyamoya syndrome from MMD, high-resolution MR imaging has been used to help identify atherosclerosis as a potential underlying origin (Figure 3). Using 3-T MR to evaluate a patient presenting with multiple ischemic stokes who had supraclinoid internal carotid artery stenosis with associated moyamoya type collaterals on digital subtraction angiography, we reported that T1-weighted, T2-weighted, 3-dimensional time-of-flight, and proton-density--weighted images could identify a diseased portion of the internal carotid artery that was severely narrowed secondary to thickened intima (very different from the atrophic vessel wall seen in idiopathic MMD). This MR finding, combined with the patient’s history of dyslipidemia, hypertension, and coronary artery disease, led to the diagnosis of moyamoya phenomenon secondary to underlying atherosclerosis.52

Regarding techniques to aid surgical revascularization, virtual surgical planning systems using 3-dimensional digital subtraction angiography to precisely locate appropriate recipient and donor vessels to make smaller and less invasive craniotomies during surgical revascularization have recently been explored. This novel preoperative planning technique was recently reported in a series of 28 patients, including 6 with MMD.53 Virtual surgical planning with MR angiography and computed tomographic angiography has also been described.54

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Surgical revascularization has been the mainstay of treatment for moyamoya patients for years. For patients with ischemic symptoms, hemodynamic disturbances rather than thromboembolic events are thought to be the principal underlying cause; therefore, a variety of surgical procedures have been devised to augment CBF distal to the area of steno-occlusion and to decrease the risk of further ischemic events. For patients with hemorrhagic symptoms, similar surgical procedures have been used with the hope that augmentation of CBF will ultimately lead to a reduction in the fragile moyamoya collaterals and a decrease in further hemorrhagic events. These procedures fall into 2 categories: direct revascularization, in which a scalp artery or other extracranial vessel is sewn directly to a cortical artery in an effort to provide immediate increase in CBF, and indirect revascularization, in which vascularized tissues are applied to the cortical surface in an effort to promote angiogenesis and to improve CBF over time. The most common of these procedures are described below.

Donaghy and Yaşargil55 introduced the superficial temporal artery (STA)--to--middle cerebral artery (MCA) bypass in 1968. It is commonly performed for the treatment of MMD (Figure 4).56 Briefly, the course of the STA is mapped with a Doppler flow probe, and the posterior limb of the STA is usually selected. The STA is dissected free along with a small cuff of galea connective tissue, and a small craniotomy centered over the distal aspect of the sylvian fissure is performed. The dura is opened, and an M4 branch of the MCA is selected. The donor STA and recipient M4 branch are then temporarily clipped, prepared, and anastomosed in end-to-side fashion with 10-0 interrupted or running sutures. The temporary clips are removed, and graft patency is confirmed by use of intraoperative catheter angiography or, more recently, indocyanine green videoangiography or perivascular flow probe as explained below.

The most common indirect procedures include encephaloduroarteriosynangiosis (EDAS), encephaloduroarteriomyosynangiosis, and multiple burr holes. All are designed to promote the formation of extracranial to intracranial collaterals over a period of months to ultimately achieve revascularization of the cerebral hemisphere. For EDAS (Figure 5), the STA and accompanying cuff of galea connective tissue are exposed in a manner that preserves STA inflow and outflow.56 This arterialized tissue is then overlaid and sutured onto the brain surface. For encephaloduroarteriomyosynangiosis, the STA and accompanying cuff of galea connective tissue are overlaid and sutured onto the brain surface in conjunction with a pedicle of temporalis muscle. For multiple burr holes, 10 to 20 burr holes are placed over each affected hemisphere, and the underlying dura is incised and separated.57 Although used predominantly in children, this technique has also been reported with successful results in adults.57

The primary goal of surgical revascularization for moyamoya is to decrease the incidence of future ischemic and hemorrhagic events. A secondary goal in some patients is improvement in cognitive function because chronic cerebral ischemia can cause significant cognitive impairment in some moyamoya patients.58 Because large-scale randomized controlled trials comparing surgical and medical management in moyamoya patients have yet to be performed, medical decision making for this population currently relies on data obtained from nonrandomized prospective and retrospective clinical studies that have examined patient outcome after surgery vs medical therapy.

The efficacy of surgical intervention in slowing the rate of decline in the pediatric population has been studied in both the Japanese and North American populations. In 1 Japanese study, of 23 moyamoya patients who underwent surgical intervention (both indirect, and combined direct/indirect techniques) and had > 5 years of follow-up, 16 had good outcomes and were living normal daily lives as students or employees and 7 had fair outcomes, with 2 adolescents performing simple jobs because of their mental retardation, 1 student going to a high school for handicapped individuals, and 4 students with subpar performance in regular schools.59 In 1 series of 126 North American patients treated with pial synangiosis, at the 1-year follow-up, 90 were independent without any significant disability, 13 were independent with mild neurological deficit, 14 had moderate disability and required some help with ambulation, 6 had moderate to severe neurological disability and were unable ambulate, 2 were dead (1 invasive meningioma and 1 intracerebral hemorrhage), and 1 was lost to follow-up.60 Results from these studies, when compared with the expected natural history of this condition, suggest that surgical intervention in pediatric moyamoya patients likely leads to reduced ischemic neurological events and better overall patient outcome.

Asian studies in adults have focused primarily on the incidence of future hemorrhagic events, given that this is the predominant mode of presentation in this population. Liu and colleagues61 performed a retrospective analysis of 97 consecutive patients with hemorrhagic MMD who were treated with either conservative or surgical management. After a median follow-up of 7.1 years, 21 of these 97 patients (21.7%) developed a second episode of bleeding, and 6 patients (6.2%) died as a result of the hemorrhage. Median interval from presenting hemorrhage to subsequent rebleeding was 9.1 years (range, 0.1-23.2 years). A significant difference in rebleeding rates between patients treated conservatively and those treated with surgery was noted; 17 of 43 conservatively treated patients (37.1%) vs 4 of 54 surgically treated patients (7.4%) experienced rebleeding in long-term follow-up (odds ratio, 8.1; 95% confidence interval, 2.4-26.8; P < .001). This difference was also significant via Kaplan-Meier analysis. Moreover, the rebleeding rate in patients who underwent direct bypass was lower than that in patients treated with indirect bypass alone (0% vs 28.5%; 95% confidence interval, 1.0-1.9; P = .002). Similar results have been reported by other retrospective studies from Asia.28,62,63 In total, these retrospective data suggest that surgical revascularization likely reduces the incidence of rehemorrhage in patients with hemorrhagic MMD. This premise is currently being tested in the Japan Adult Moyamoya Trial, a prospective, multicenter, randomized controlled trial of STA-to-MCA bypass vs medical therapy for hemorrhagic MMD.64

North American studies have focused primarily on the incidence of future ischemic events, given that this is the primary mode of presentation for North Americans with moyamoya, both adults and children. Guzman et al65 retrospectively analyzed a consecutive case series of 329 North American patients with moyamoya, 233 of whom were adults who underwent 389 procedures and 96 of whom were children who underwent 168 procedures. The majority of these patients presented with ischemic stroke or TIA, and the preferred surgical approach was direct surgical bypass. They reported operative morbidity and mortality rates of 3.5% and 0.7% per treated hemisphere, respectively. The cumulative 5-year risk of perioperative or subsequent stroke or death was 5.5%. Scott et al16,60 retrospectively analyzed a consecutive case series of 143 moyamoya patients, all of whom were children who underwent 271 procedures. The majority of these patients presented with ischemic stroke or TIAs, and all underwent indirect revascularization via a modified EDAS technique. The reported operative morbidity was 4% per treated hemisphere. In the 126 patients with > 1 year of clinical follow-up, 4 suffered late-onset ischemic stroke. These reported rates of recurrent ischemic stroke after surgical revascularization compare very favorably to the expected natural history of North American moyamoya.

Other studies have examined outcome in surgically vs conservatively treated patients with moyamoya in an effort to more directly assess the efficacy of surgical revascularization for North American moyamoya patients. Starke et al66 retrospectively analyzed 43 adult North American patients who were predominantly women (65%) and white (65%), had presented with ischemic symptoms (98%), and had bilateral disease (86%). Nineteen patients underwent unilateral and 24 patients underwent bilateral EDAS procedures (67 treated hemispheres, 17 untreated hemispheres). Periprocedural infarction occurred in 3% of the treated hemispheres. The 5-year infarction-free survival rate was 94% in the surgically treated hemispheres vs < 36% in the untreated hemispheres (P = .007). After controlling for age and sex, infarction was 89% less likely to occur in the surgically treated hemispheres than in the contralateral hemispheres (hazard ratio, 0.11, 95% confidence interval, 0.02-0.56). Hallemeier et al13 retrospectively analyzed 34 North American adults with moyamoya who were predominantly women (73%) and white (68%), had presented with ischemic symptoms (71%), and had bilateral disease (65%). Fourteen patients were treated with surgical revascularization (20 treated hemispheres, 48 untreated hemispheres). Periprocedural infarction occurred in 10% of the treated hemispheres. In a comparison of symptomatic cerebral hemispheres, the 5-year risk of recurrent ipsilateral stroke was significantly greater in medically treated (65%) vs surgically treated (17%) patients. In total, these retrospective data suggest that surgical revascularization likely reduces the incidence of recurrent ischemia in patients with ischemia MMD.

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A critical component of surgical revascularization for moyamoya is the maintenance of hemodynamic stability through the induction of anesthesia, the surgical procedure itself, and emergence from anesthesia. This cannot be overemphasized given the tenuous cerebral hemodynamic state of moyamoya patients, often in both cerebral hemispheres. Although no specific anesthetic technique has been definitively shown to decrease perioperative complications in moyamoya patients, several methods for optimizing intraoperative cerebral hemodynamics are commonly used to help minimize this risk. First, intravenous anesthetics as opposed to inhalation agents are typically because used the latter have been associated with reduced regional CBF in moyamoya patients,67 which could increase the risk for cerebral steal syndrome and perioperative ischemic complications. Second, mean arterial blood pressure is maintained about 10% above preoperative baseline throughout the surgical procedure. Third, as opposed to most cranial procedures in which hypocarbia is used to achieve brain relaxation through global cerebral vasoconstriction, exquisite maintenance of normocarbia throughout the procedure is essential to minimizing the risk for ischemic complications. Fourth, also unlike most cranial procedures, mannitol is avoided to maintain adequate intravascular volume throughout the procedure. Other anesthetic techniques that can be considered include use of intraoperative somatosensory evoked potential and electroencephalogram monitoring to detect impaired cortical perfusion that would require additional blood pressure adjustments and the use of barbiturates to induce electroencephalogram burst suppression and to reduce metabolic demand of the brain during temporary artery occlusion for the anastomosis. Given the importance of adhering to these anesthetic principles and the dire consequences that can result when deviations from these principles occur, we refer to the heightened attention paid to maintaining intraoperative cerebral hemodynamics in this population as moyamoya paranoia.

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Several advances pertaining to the surgical procedure itself have occurred in recent years. One is the introduction of indocyanine green videoangiography into the armamentarium for evaluating graft patency and flow at the time of anastomosis. Indocyanine green is injected intravenously, and as it passes through the anastomosis, it is excited by near-infrared light and visualized as it emits near-infrared fluorescence. Its use was recently examined for direct bypass in 40 patients, 18 of whom had MMD.68 In this series, 4 nonfunctioning bypasses were identified intraoperatively and corrected. In every case, the intraoperative findings using indocyanine green were validated postoperatively with computed tomographic angiography or digital subtraction angiography.68

Another advance is the application of an intraoperative perivascular flow probe that uses ultrasonic transit-time principles to directly measure blood flow (rather than velocity) to assess the patency and flow of a direct bypass. This involves positioning a flexible perivascular flow probe around the donor and recipient vessels to calculate the direction and rate of flow in milliliters per minute. In moyamoya patients, perivascular flow probe measurements have been used in 2 ways. First, a cut flow index has been devised to help assess bypass patency. The cut flow index is calculated by first measuring “cut flow” through the cut end of the STA (before the anastomosis) and then measuring “bypass flow” through the STA once the anastomosis is complete (cut flow index = bypass flow/cut flow). A cut flow index of <0.5 is highly correlated with a poorly functioning bypass and indicates that a revision is necessary.69 Second, postanastomotic MCA flow can be used to help predict postoperative complications because identification of high postanastomotic flow is correlated with the incidence of postoperative TIA, ischemic stroke, and intracranial hemorrhage.70

Finally, there have been efforts to reduce or eliminate the ischemia time during construction of a surgical bypass with the idea that this might reduce perioperative ischemic complications. One such technique is the excimer laser--associated nonocclusive anastomosis. This involves sewing a platinum ring into a donor vessel, which is then attached to the recipient vessel. A laser catheter is then inserted through a slit in the donor vessel and used to make the arteriotomy. The advantage of this technique is that there is no need for temporary occlusion of the recipient vessel. Currently, excimer laser--associated nonocclusive anastomosis can be used only for vessels > 2.5 mm, but attempts are being made to apply it to smaller-diameters vessels such as that seen with STA-to-MCA bypass procedures.45,71 Another approach to reduce temporary artery occlusion time during bypass is the use of an automated anastomosis system that can complete a vascular anastomosis within seconds. One such system (the C-Port Flex-A Anastomosis System, Cardica, Inc) has been successfully used in humans for high-flow bypasses (Figure 6).72,73 However, modifications to the device will be required to permit its use for STA-to-MCA bypass procedures.

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Recent investigations have shed light on the natural history of MMD, its pathophysiology, the role of radiologic imaging, and techniques to improve surgical interventions and outcomes. Novel techniques have been developed to guide patient selection, preoperative planning, intraoperative monitoring and bypass assessment, and postoperative follow-up. Future investigations that focus on the natural history of the disease and further development of novel technologies to improve the preoperative and intraoperative techniques should help guide future surgical management of patients with moyamoya.

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The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.

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Cerebral revascularization; Hemorrhagic stroke; Ischemic stroke; Moyamoya; Natural history; STA-MCA bypass

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