| Edward R Smith MD, R. Michael Scott MD |
Department of Neurosurgery, Children's Hospital Boston / Harvard Medical School, Boston, USA; E-mail: edward.smith@childrens.harvard.edu
Published: 6 May 2007
Abstract
Moyamoya syndrome is a progressive vasculopathy characterized by narrowing of the intracranial segments of the internal carotid arteries and the subsequent development of abundant collateral vessels with the angiographic appearance of a puff of smoke – “moyamoya” in Japanese. Clinically, patients with moyamoya present with symptoms of cerebral ischemia (common in children), intracranial hemorrhage (common in adults), headache or seizure. The rate of progression of the disease is variable, with some patients having only rare, intermittent transient ischemic attacks (TIAs) and others presenting with a fulminant course marked by rapid neurologic decline. Regardless of presentation, the disease follows a relentlessly progressive course if left untreated.
Some authors have distinguished between moyamoya disease, the idiopathic form of moyamoya, and moyamoya syndrome, defined as the vasculopathy found in conjunction with systemic conditions such as heart disease, Down syndrome and others. In both moyamoya disease and moyamoya syndrome, treatment strategies are directed toward improving cerebral blood supply. Medical management is an important adjunct in improving the outcomes of patients with moyamoya, but definitive treatment of the disease requires surgical revascularization.
Introduction
Moyamoya syndrome is a vasculopathy characterized by chronic progressive stenosis to occlusion at the apices of the intracranial internal carotid arteries, including the proximal anterior cerebral arteries and middle cerebral arteries. It has been associated with approximately 6% of childhood strokes (1,2). This progressive stenosis occurs simultaneously as characteristic arterial collateral vessels develop at the base of the brain. These collateral vessels, when visualized on angiography, have been likened to the appearance of "something hazy, like a puff of cigarette smoke drifting in the air," – which translates to “moyamoya” in Japanese.
Some authors have distinguished between moyamoya disease, the idiopathic form of moyamoya, and moyamoya syndrome, defined as the vasculopathy found in association with another condition, such as neurofibromatosis, sickle cell disease, or Down syndrome (3,4). In addition, the use of the term “angiographic moyamoya” has been proposed as a unifying diagnosis based solely on angiographic findings (5). The precise etiology of this vasculopathy remains unclear, but its progressive course, coupled with a good response to surgical therapy, has resulted in study of this entity in far greater detail than might be expected from its relative rarity.
Epidemiology
First described in Japan, moyamoya syndrome has now been observed throughout the world and affects individuals of many ethnic backgrounds, with increasing detection of this disease in American and European populations (6,7). In Japan, it is the most common pediatric cerebrovascular disease, affecting females almost twice as much as males with a prevalence of approximately 3/100,000 (1,8). In Europe, a recent study cited an incidence of 0.3 patients per center per year, which is approximately one-tenth of the incidence in Japan (9). A 2005 U.S. study suggests an incidence was 0.086/100,000 persons. The ethnicity-specific incidence rate ratios compared to whites were 4.6 (95% CI: 3.4 to 6.3) for Asian Americans, 2.2 (95% CI: 1.3 to 2.4) for African Americans, and 0.5 (95% CI: 0.3 to 0.8) for Hispanics (10).
In the United States and Korea, reports corroborated historical claims of a bimodal age distribution of moyamoya, one group in the pediatric age range (around the first decade of life) and a second group of adults in the 30-40 year old range. Both groups found that children were more likely to present with ischemic events (either strokes or transient ischemic attacks (TIAs)) than hemorrhage, more common in the adult group (11, 12). Adult moyamoya patients often present with hemorrhage, leading to rapid diagnosis. In contrast, children usually present with transient ischemic attacks (TIAs) or strokes, which may prove more difficult to diagnose because of patient’s inadequate verbal skills, leading to delayed recognition of the underlying moyamoya (3,13). Overall, most children present with recurrent transient ischemic attacks, stroke, seizures, or headaches; only about 3% of pediatric patients in The Children’s Hospital, Boston series had an intracerebral hemorrhage as their first symptom (3). The natural history of this disease is unpredictable.
Table 1
Associated Conditions
There are a number of clinical conditions which have been associated with moyamoya (14). These include prior radiotherapy to the head or neck for optic gliomas, craniopharyngiomas, and pituitary tumors; genetic disorders, such as Down syndrome, neurofibromatosis type I (NF1) (with or without hypothalamic-optic pathway tumors), large facial hemangiomas, sickle cell anemia and other hemoglobinopathies; auto-immune disorders such as Graves’ Disease; congenital cardiac disease; renal artery stenosis; meningeal infections, including tuberculous meningitis; and a host of unique syndromes such as Williams, Alagille. Table 2 summarizes the clinical associations noted in a recently published series (60).
Table 2
Natural History and Prognosis
The prognosis of moyamoya syndrome is difficult to predict because the natural history of this disorder is not well known. The progression of disease can be slow, with rare, intermittent events, or can be fulminant, with rapid neurologic decline (3,14). However, regardless of the course, it seems clear that moyamoya syndrome, both in terms of arteriopathy and clinical symptoms, inevitably progresses in untreated patients (15). It has been estimated that 50-66% of patients with moyamoya have progression of the disease with poor outcomes if left untreated (16-18). This number contrasts strikingly to an estimated rate of only 2.6% of disease progression in a recent meta-analysis of 1,156 surgically treated pediatric patients (19). A more recent review of asymptomatic patients reported an annual stroke rate of 3.2% and reported progression of disease in 80% (20). The experience of Children’s Hospital Boston has been that approximately 55-67% of patients will demonstrate radiographic progression of disease within a 5 year period.
Overall prognosis of patients with moyamoya syndrome depends on the rapidity and extent of vascular occlusion, the patient’s ability to develop effective collateral circulation, the age at onset of symptoms, the severity of presenting neurological deficits and degree of disability, and the extent of infarction seen on computed tomography or magnetic resonance imaging studies at the time of initial presentationn (21). In general, neurologic status at time of treatment, more so than age of the patient, predicts long term outcome (3, 22).
Importantly, if surgical revascularization is performed prior to disabling infarction in moyamoya syndrome, even if severe angiographic changes are present, the prognosis tends to be excellent (3). Even in asymptomatic patients, surgical revascularization has been reported to protect against infarction (20). However, if left untreated, both the angiographic process and the clinical syndrome invariably progress, producing clinical deterioration with potentially irreversible neurological deficits over time (23).
Screening
Although there are no broad-based initiatives supporting screening protocols for moyamoya syndrome, particular note should be made of the association of moyamoya with NF1, Down syndrome, sickle cell disease and in patients who have been treated with cranial irradiation for brain tumors. These diseases are relatively common in pediatric practice and individual reports support the premise of prospective non-invasive screening for moyamoya syndrome in these selected populations (4,24-29). There is less compelling evidence to suggest some utility to screening first degree relatives of patients with moyamoya. The familial incidence of affected first-degree relatives in Japan is 7-12% and a similar rate of approximately 6% was found in the Children’s Hospital, Boston, series (3,30-32). Despite these relatively small percentages, the compelling association between neurologic status at presentation and long term outcome after treatment may support a more aggressive posture toward screening in this population (3).
Diagnostic Investigations
Moyamoya syndrome should be considered and diagnostic evaluation begun in any child who presents with symptoms of cerebral ischemia (e.g., a transient ischemic attack manifesting as episodes of hemiparesis, speech disturbance, sensory impairment, involuntary movement, and/or visual disturbance), especially if the symptoms are precipitated by physical exertion, hyperventilation, or crying. The diagnosis of moyamoya is confirmed by radiographic studies. Signs of moyamoya can be direct, such as the characteristic arterial narrowing and “puff of smoke” collaterals, or can be indirect, such as evidence of cerebral hypoperfusion or multiple infarcts. Radiographic evaluation of a given patient suspected of having moyamoya usually proceeds through several studies.
The workup of a patient in whom the diagnosis of moyamoya syndrome is suspected typically begins with a either a magnetic resonance imaging (MRI) study or computerized tomography (CT) of the brain. On CT, small areas of hypodensity suggestive of stroke are commonly observed in cortical watershed zones, basal ganglia, deep white matter or periventricular regions (33, 34). Although rare in children, hemorrhage from moyamoya vessels can be readily diagnosed on head CT, with the most common sites of hemorrhage being the basal ganglia, ventricular system, medial temporal lobes, and thalamus.
Patients with these findings on CT are often subsequently evaluated with a MRI/MRA. Acute infarcts are well seen using diffusion weighted imaging (DWI), chronic infarcts are better delineated with T1 and T2 imaging and cortical ischemia may be inferred from FLAIR sequences which demonstrate linear high signal following a sulcal pattern, felt to represent slow flow in poorly-perfused cortical circulation (35). Most suggestive of moyamoya on MRI is the finding of diminished flow voids in the internal carotid and middle and anterior cerebral arteries coupled with prominent collateral flow voids in the basal ganglia and thalamus. These imaging findings are virtually diagnostic of moyamoya syndrome (34,36-40).
Because of the excellent diagnostic yield and noninvasive nature of MR imaging, it has been proposed that MRA be used as the primary diagnostic imaging modality for moyamoya syndrome instead of conventional cerebral angiography (36,41-45). While MRA affords the ability to detect stenosis of the major intracranial vessels, visualization of basal moyamoya collateral vessels and smaller vessel occlusions is frequently subject to artifact. Therefore, to confirm the diagnosis of moyamoya syndrome and to visualize the anatomy of the vessels involved and the patterns of flow through the hemispheres, conventional cerebral angiography is typically required.
Angiography should consist of a full four vessel series, including selective injection of the external carotid systems (both internal carotid arteries, external carotid arteries and vertebral arteries). External carotid imaging is essential to identify preexisting collateral vessels, so that surgery, if performed, will not disrupt them. Aneurysms or AVMs, known to be associated with some cases of moyamoya, can also be best detected by conventional angiography. In a study of 190 angiograms of pediatric patients, the risk of complications from performing angiography in children with moyamoya syndrome has been demonstrated to be no higher than the risk of performing angiography in non-moyamoya populations being evaluated for cerebrovascular disease (46).
It is important to note the utility of peri-procedural hydration for these patients along with aggressive measures to control pain and anxiety. Crying can lower pCO2, with resultant cerebral vasoconstriction and a subsequent increased risk of stroke. Class III data supports the utilization of these measures, with studies demonstrating decreased frequency of TIAs and strokes when patients are treated with these techniques (47). In addition, the risk of angiography is increased in patients with sickle cell disease due to the contrast load on the kidneys. As such, it is recommended that these patients undergo pre-angiography exchange transfusion and pre-procedural hydration when feasible (48).
Cerebral blood flow studies, utilizing techniques such as transcranial Doppler ultrasonography (TCD), xenon-enhanced CT, positron emission tomography (PET), and single photon emission computed tomography (SPECT) with acetazolamide challenge, also can be helpful in the diagnostic evaluation of patients with moyamoya syndrome as well as assisting in treatment decisions. For example, transcranial Doppler examination provides a noninvasive way to follow changes in blood flow patterns over time in larger cerebral vessels, while xenon CT, PET, and SPECT can be used both to detect regional perfusion instability prior to treatment and to determine the extent of improvement of functional perfusion after therapy (49-57).
There is compelling data to support the use of TCD as an initial screening study for stroke in the sickle cell population. A recent randomized trial, the stroke prevention trial in sickle cell anemia (STOP) evaluated over 2000 children with sickle cell disease and validated the use of TCD as a screening study for stroke in this patient group (58). Use of the information gained from these TCD studies resulted in a > 90% decreased risk of strokes through the use of transfusions (59). Although this trial was not primarily focused on moyamoya disease, the anticipated widespread use of TCDs will likely increase the number of MRI/A studies in this population, with a corresponding increase in the number of diagnosed cases of sickle cell-related moyamoya.
Although each of these studies has the potential to add information in the diagnosis and management of moyamoya, not all are routinely used in the United States. MRI/A and conventional angiography are the standard diagnostic tools utilized for most patients with moyamoya; following surgical treatment, an angiogram and an MRI/MRA are often obtained one year after operation, and depending on the age of the patient, subsequent yearly MR imaging. The role of SPECT and PET scans in the evaluation and management of moyamoya syndrome has been increasing over the past decade (55,57). Further studies and increased availability are needed to improve utilization of these modalities.
In addition to radiographic evaluation of patients with moyamoya syndrome, there is limited data supporting the practice of screening patients who have been diagnosed with moyamoya syndrome for coagulation disorders. In a prospective study of 10 patients, with evaluations of protein C, protein S, antithrombin, plasminogen, activated protein C resistance, factor V Leiden, prothrombin gene mutations, lupus anticoagulant, anticardiolipin antibodies, and anti-beta(2)-glycoprotein I antibodies, 40% had abnormal results (60). Although a small study, the relative non-invasiveness of the testing, coupled with the potential ability to treat a number of these coagulation disorders which might otherwise increase the risk of strokes in the affected patient, support the practice of screening for these conditions in moyamoya patients.
Treatment Considerations
Once a major stroke or hemorrhage has occurred, children with moyamoya syndrome frequently are left with permanent neurologic impairment (14,61). Therefore, early diagnosis and prompt treatment of this disorder are of utmost importance in order to prevent additional neurologic deficits. Despite this urgency, there is no agreed-upon method of treatment for patients with this chronic occlusive cerebrovascular disorder. There are reports of some patients who stabilize clinically without intervention, but this typically occurs after they have experienced significant, debilitating neurologic disability.
The majority of data available supports the use of surgical revascularization as a first-line therapy for the treatment of moyamoya syndrome, particularly for patients with recurrent or progressive symptoms (19). Some studies have suggested that there may be differences in the effectiveness of surgery for the treatment of moyamoya depending on the type of presentation of the patient – hemorrhagic or ischemic. However, the papers that do cite a difference suggest that the ischemic presentation subtype is responds more favorably to surgery than does the hemorrhagic subtype, and the majority of pediatric moyamoya patients present with ischemic symptoms (62). Two relatively large studies with long-term follow up have demonstrated a good safety profile for surgical treatment of moyamoya (4% risk of stroke within 30 days of surgery per hemisphere) with a 96% probability of remaining stroke-free over a 5 year follow-up period (3, 62). This data suggests that surgical therapy of moyamoya confers an effective, durable treatment for the disease.
Historically, there has been a paucity of head-to-head data comparing the efficacy of medical versus surgical therapy for moyamoya. A large survey in 1994 from Japan noted that among 821 registered patients with moyamoya, there were no significant differences in outcome between medically and surgically treated patients (63). However, more recent data suggests that a high percentage, 38.4% (out of a group of 651), of moyamoya patients who are not initially treated with surgery eventually come to surgery as a result of progressive symptoms(64). Medical therapy is often used as treatementtreatment for moyamoya syndrome, particularly when the patient is a poor operative risk (severe cardiac disease, advanced debilitation from stoke burden or other severe co-morbidities) or has relatively mild moyamoya disease. However, a recent meta-analysis noted that medical therapy should not be employed for the treatment of patients with progressive neurologic symptoms, stating that, “medical treatments (for example, vasodilators, low molecular dextrans and steroids) are ineffective.” (19).
Indications for Surgery
Any child with a diagnosis of moyamoya syndrome should be considered for surgical therapy, such as pial synangiosis. The condition is invariably progressive, both clinically and radiographically, and permanent deficits can occur while patients are being observed to verify the syndrome's progressive nature.
The quality of evidence complied in a recent meta-analysis of 1,448 patients from 57 studies in the English language led to recommendations based on case series and expert opinions (19). The review noted multiple difficulties with objectively assessing the efficacy of surgery, including the limited data on the natural history of moyamoya as a comparison, the absence of head-to-head trials comparing treatments, the lack of universally accepted indications for surgery, the wide variation in surgical techniques, the potentially subjective nature of clinical outcome measures, the paucity of more objective outcome data (such as stringent demonstration of post-surgical improved vascularization or perfusion) and the small number of studies with long-term follow-up. With these caveats, the analysis concluded that “the data from the medical literature suggest that surgical revascularization is a safe intervention for pediatric moyamoya syndrome and most treated patients derive some symptomatic benefit.”(19).
Indications for surgery were noted in less than 15% of studies and varied between centers (19). General indications and timing of surgery remain controversial (65, 66). Quotes from the meta-analysis regarding indications for surgery include: “neurological signs and symptoms likely to be related to cerebral ischemia and angiographic documentation of moyamoya disease”, “repeated ischemic attacks or progressive mental retardation”, “low cerebral blood flow in the frontal or occipital area, frontal or occipital atrophy on CT” , “transient weakness or hypoperfusion”, “inexorable progression of symptoms”, “symptomatic/decreased hemodynamic reserve on cerebral blood flow study”, “recurrent TIA and/or stroke after first operation” and “ischemic” symptoms.” (19).
Recent guidelines from Japan’s Ministry of Health and Welfare regarding indications for surgical treatment of moyamoya state: “In the cases with (1) repeated clinical symptoms due to apparent cerebral ischemia, or (2) a decreased regional cerebral blood flow, vascular response and perfusion reserve, based on the findings of a cerebral circulation and metabolism study, surgery is indicated.” (63,67) However, the guidelines are unclear regarding the timing of surgery, except to state that patients who present with acutely symptomatic hemorrhage may require emergency operative decompression or cerebrospinal fluid diversion.
Medical Treatment
There is no known medical treatment capable of reversing the progression of moyamoya syndrome. However, there is support for the use of two classes of medications to slow the progression of the disease; anticoagulants/anti-platelet agents and vasodilators
The antiplatelet effect of aspirin is useful in moyamoya because some ischemic symptoms appear to occur as a consequence of emboli from microthrombus formation at sites of arterial stenoses (3,61,66). Children with moyamoya are treated with lifelong aspirin therapy, with those less than 6 years of age receiving 81 mg/day and at a variable dose in older children, depending on the presence or absence of symptoms (3). While anticoagulants like warfarin are rarely used due to the difficulty of maintaining therapeutic levels in children, the use of low dose low-molecular weight heparin (Lovenox) has been used, at 0.5 mg/kg twice a day subcutaneously for selected children, particularly those children who are neurologically unstable and need rapidly-reversible anticoagulation prior to procedures such as surgery or angiography that preclude aspirin use (68; Smith, Scott, unpublished data). In these cases, the aspirin is held for ten days prior to the procedure and the heparin is employed as a “bridge” to provide some protection which has a shorter pharmacologic half-life than aspirin. After the procedure is completed, aspirin is usually restarted.
The other medication class that has been useful in the treatment of certain symptoms in moyamoya syndrome is calcium channel blockers (61). These drugs may be particularly useful in ameliorating symptoms of intractable headaches or migraines, commonly seen in moyamoya patients, and also seems to be effective in reducing both the frequency and severity of refractory TIA.
Surgical Treatment
There are a number of studies in the literature that support a role for surgical management of moyamoya disease, and surgery is generally recommended for the treatment of patients with recurrent or progressive cerebral ischemic events and associated reduced cerebral perfusion reserve. Many different operative techniques have been described, all with the main goal of preventing further ischemic injury by increasing collateral blood flow to hypoperfused areas of cortex, using the external carotid circulation as a donor supply (3, 14).
Various bypass procedures have been performed in the treatment of moyamoya disease, which can generally be divided into direct and indirect types. Direct anastomosis procedures, most commonly superficial temporal artery (STA) to middle cerebral artery (MCA) bypasses, may achieve instant improvement in focal cerebral perfusion, but these procedures are often technically difficult to perform because small pediatric patients often do not have a large enough donor scalp artery or recipient middle cerebral artery to allow for a anastomosis large enough to supply a significant amount of additional collateral blood supply.
A variety of indirect anastomotic procedures have been described: encephaloduroarteriosynangiosis (EDAS) whereby the STA is dissected free over a course of several inches and then sutured to the cut edges of the opened dura; encephalomyosynangiosis (EMS) in which the temporalis muscle is dissected and placed onto the surface of the brain to encourage collateral vessel development; and the combination of both, encephalo-myo-arterio-synangiosis (EMAS) (69-73). There are multiple variations of these procedures, including solely drilling burr holes, without vessel anastomosis (74,75), and craniotomy with inversion of the dura in hopes of enhancing new dural revascularization of the brain (76). Cervical sympathectomy and omental transposition or omental pedicle grafting have also been described, although sympathectomy has largely been abandoned due to its ineffectiveness (69, 73, 77-86). Finally, a number of groups have reported improved results in the use of combined direct and indirect anastamoses (64, 69, 73, 79). A modification of the EDAS procedure has been described to treat moyamoya syndrome in both children and adults termed “pial synangiosis,” which leads to the induction of new collateral vessels in the patient with chronic ischemia due to moyamoya (3). The efficacy and durability of this variant of indirect revascularization has been validated by the largest surgical series of pediatric moyamoya patients reported in North America (3).
One major consideration is the decision of which surgical technique to employ. A recent meta-analysis of 1,156 pediatric moyamoya patients treated with surgery concluded that 87% (1,003 patients), derived symptomatic benefit from surgical revascularization (complete disappearance or reduction in symptomatic cerebral ischemia), but that there was no significant difference between the indirect and direct/combined groups (19). Guidelines from Japan’s Ministry of Health and Welfare regarding indications for the surgical treatment of moyamoya syndrome only discuss bypass surgery for revascularization – a technique which is often not feasible in small children due to the small caliber of their vessels (63, 67). A review of pediatric patients with moyamoya has proposed that children under the age of 8 years should all receive indirect revascularization surgery, while older children should potentially receive both direct and indirect revascularization (if feasible) (64).
Once the decision for surgical therapy has been made, several perioperative considerations need to be addressed. In addition to the general issues regarding surgery in children, moyamoya patients are at particular risk of ischemic events in the perioperative period. Crying and hyperventilation, common occurrences in children at times during hospitalization, can lower pCO2 and induce ischemia secondary to cerebral vasoconstriction. Any techniques to reduce pain – including the use of perioperative sedation, painless wound dressing techniques, and absorbable wound suture closures – helped to reduce the incidence of strokes, TIAs and length of stay in a recent study (87). A further perioperative consideration is the use of monitoring, such as intraoperative EEG or near-infrared spectroscopy, used to identify and ameliorate ischemic events detected while the patient is under general anesthesia.
Peri- and intra-operative considerations
Risks of surgery are more often related to neurologic instability of the patient at the time of surgery and to the risks of anesthesia rather than to actual surgical manipulations. The administration of general anesthesia can result in transient, but significant, physiologic changes which can affect cerebral blood flow. Blood pressure, blood volume and PaCO2 require careful monitoring because moyamoya patients have a diminished cerebral perfusion reserve and deviation from normal levels can result in stroke (87).
To reduce the risk of intraoperative and perioperative neurologic morbidity, therefore, meticulous management of the patient is required to avoid hypotension, hypovolemia, hyperthermia, and hypocarbia both intraoperatively as well as perioperatively (3 ). As noted above, intraoperative EEG monitoring with a full array of scalp electrodes can be helpful in the neurologic assessment of patients under general anesthesia. To help prevent hypovolemia during surgery, patients are often admitted the evening prior to surgery for aggressive intravenous hydration. Postoperatively, the patients are hydrated with intravenous fluids at one and one-half the normal maintenance rate based on weight for 48-72 hours. Aspirin is given on the first postoperative day.
There is no evidence that one anesthetic agent or technique is superior in patients with moyamoya syndrome. Muscular blockade is established by a nondepolarizing muscle relaxant prior to intubation. Any fluid deficits are partially replaced by intravenous crystalloid without glucose (10 ml/kg) over 15 minutes after induction. Anesthesia is maintained with low-dose isoflurane and a balanced nitrous oxide/oxygen mixture with fentanyl. The rationale for the use of these agents is that isoflurane is a cerebral vasodilator and may even provide a protective effect against ischemia. However, any anesthetic technique that will maximize the balance between cerebral blood flow and oxygen consumption is probably reasonable. End-tidal CO2 is maintained between 36 and 42 mm Hg. One should avoid the use of hyperventilation or any anesthetic technique that would cause cerebral vasoconstriction, since hyperventilation in a child with compromised cerebral circulation could precipitate further ischemic sequelae. Normotension, appropriate for age, is maintained. Diuretics such as mannitol and Lasix are unnecessary and possibly risky in this patient population because of the possibility of dehydration leading to hypotension.
Potential complications associated with surgical treatment of moyamoya syndrome include postoperative stroke, subdural hematoma, both following trauma and spontaneous, andspontaneous, and intracerebral hemorrhage.
Follow-up Considerations
Careful follow-up of patients with moyamoya is warranted (63, 67, 19). Of patients treated conservatively or with medical management, 38.3% of unoperated patients required surgery eventually (64). A study of patients initially diagnosed with unilateral moyamoya found that 27% (17/64) of these patients with unilateral disease progressed to bilateral involvement, with younger patients being most commonly affected, often within 1-5 years (88). Other data further support the premise that younger children with unilateral disease commonly progress to bilateral involvement (89). The experience of Children’s Hospital Boston suggests that at least 14% of unilateral patients will progress to requiring surgery on the second side within an average of 2.2 years. Of those patients who were treated operatively,(for either bilateral or unilateral disease) the need for re-operation due to refractory disease ranged from 1.8-18% (64). These data suggest that periodic clinical and radiographic examinations of patients with moyamoya disease, even if treated, should be performed on a regular basis.
Postoperative angiograms or MRI/A studies are usually obtained twelve months after surgery and typically demonstrate MCA collateralization from both the donor STA and the meningeal arteries (3, 64). A review of one hundred and forty-three children with moyamoya syndrome treated with pial synangiosis had marked reductions in their stroke frequency after surgery, especially after the first year postoperatively. In this group, 67% had strokes preoperatively, 7.7% had strokes in the perioperative period and only 3.2% had strokes after at least one year of follow-up. The long term results are excellent, with a stroke rate of 4.3% (2 patients in a group of 46) in patients with a minimum of 5 years of follow-up (3). This work supports the premise that surgical treatment of moyamoya provides a significant protective effect against new strokes in this patient population. This premise is further supported by a recent meta-analysis of children treated surgically for moyamoya syndrome, which found that out of 1,156 patients, 1,003 (87%) derived symptomatic benefit from surgical revascularization (complete disappearance or reduction in symptomatic cerebral ischemia) (19).
Conclusions
Moyamoya syndrome is an increasingly recognized entity which is associated with cerebral ischemia. Diagnosis is made on the basis of clinical and radiographic findings, including a characteristic stenosis of the internal carotid arteries in conjunction with abundant collateral vessel development. Surgical revascularization is recommended for definitive treatment of children with moyamoya syndrome. Treatment is predicated on revascularization of the ischemic brain, which can be direct (STA-MCA bypass) or indirect (including pial synangiosis). Both direct and indirect revascularization procedures can be effective in children. Direct revascularization confers immediate protection, but often is not technically feasible in children. Indirect surgical revascularization is effective in preventing strokes in children with moyamoya syndrome after 6-12 months.
Patients with moyamoya syndrome should be referred to centers with experience with this disease, as demonstrated by annual volume and availability of the resources needed to treat them, including an appropriate team of physicians and an intensive care unit familiar with the issues related to moyamoya syndrome. Careful follow-up of these patients is warranted. Despite the compelling anecdotal evidence supporting the role for surgical treatment of moyamoya syndrome, there is a profound need for further research to validate this data. Future efforts should focus on organizing widespread consensus of diagnostic and therapeutic standards of care, supported by well-designed prospective studies.
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