Rey. Argent. Neuroc. 2005; 19: 31

Actualización

MOYANIOYA SYNDROME*

Edward R. Smith, MD, R. Michael Scott, MD

Department of , The Children's Hospital, Boston

RESUMEN

El síndrome de Moyamoya es una vasculopatía caracterizada por la estenosis crónica y progresiva de la arteria carótida interna intracraneal. El diagnóstico se realiza en base a hallazgos clínicos y radiológicos que incluyen la muy característica estenosis de la carótida interna con un importante desarrollo de circulación colateral. Los pacientes adultos con Moyamoya con frecuencia se presentan con cuadros hemorrágicos. En cambio, los niños usualmente presentan ataques isquémicos transitorios (AIT) o infartos isquémicos y en ellos es frecuente un diagnóstico más tardío del síndrome Moyamoya. La progresión de la enfermedad puede ser lenta con eventos intermitentes o puede ser fulminante, con un rápido deterioro neurológico. Cualquiera sea laforma de evolucionar, el síndrome de Moyamoya suele presentar un empeoramiento clínico y radiológico progresivo en los pacientes no tratados. La cirugía es recomendada para el tratamiento de pacientes con eventos isquémicos cerebrales recurrentes o progresivos que presentan una reducción de la reserva de perfusión cerebral. Múltiples técnicas operatorias han sido descriptas con el propósito de prevenir injurias cerebrales isquémicas mediante un aumento del flujo sanguíneo colateral en áreas corticales hipoperfundidas utilizando la circulación carotídea externa como vascularización donante. Este trabajo discute las diferentes formas terapéuticas con un énfasis especial en la utilización de la sinangiosis pial como método de revascularización indirecta. La utilización de la sinangiosis pial es unaforma de revascularización cerebral efectiva y durable en el síndrome de Moyamoya y debe ser considerada como una forma primaria de tratamiento de esta entidad, especialmente en la población infantil. Palabras clave: accidente cerebrovascular, arteriopatía, Moyamoya, revasculariza- ción cerebral.

INTRODUCTION to "moyamoya" in Japanese. This disease was first described in the Japanese literature in 1957 when Moyamoya syndrome is a vasculopathy char- Takeuchi and Shimizu reported a case of "hypo- acterized by chronic progressive stenosis to occlu- plasia of the bilateral internal carotid arteries," sion at the apices of the intracranial internal but was first named as moyamoya 1969 by Suzuki carotid arteries, including the proximal anterior and Takaku3'4. cerebral arteries and middle cerebral arteries. It has been associated with approximately 6% of EPIDEMIOLOGY childhood strokes1 '2. This progressive stenosis occurs simultaneously as characteristic arterial First described in Japan, moyamoya syndrome collateral vessels develop at the base of the . has now been observed throughout the world.5 These collateral vessels, when visualized on an- Although considered until recently as more preva- giography, have been likened to the appearance of lent in the Asian population, it can also affect haze, a cloud or a puff of smoke - which translates individuals of many ethnic backgrounds, and there is an increasing awareness of this disease in the Arnericas and in European populations6. In Japan, * Este trabajo fue especialmente invitado para su publicación it is the most common pediatric cerebrovascular en el número especial de Revista Argentina de Neurocirugía disease, affecting females almost twice as much as dedicado al Congreso Internacional de Neurocirugía Pediátri- males'. In Europe, a recent study cited an incidence ca realizado en Buenos Aires en 2004. Debido a su arribo fuera de término, es publicado en este número. of 0.3 patients per center year,per, which is approx- Correspondencia: 300 Longwood Avenue. Boston, MA 02115 imately one-tenth of the incidence in Japan7. In the E-mail: michael. [email protected] .edu United States and Korea, reports corroborated his-

32 E.R. SMITH ET AL REV. ARGENT. NEUROC. torical claims of a bimodal age distribution of Table 1 moyamoya, one group in the pediatric age range (around the first decade of life) and a second group

97 67.8 of adults in the 30-40 year old range. Both groups TIAs (including drop attacks) 62 43.4 found that children were more likely to present with 9 6.3 ischemic events (either or transient ischem- 9 6.3 ic attacks (TIAs)) than hemorrhage, more common in Choreiform movements 6 4.2 the adult group". The goal of therapy is to arrest or 6 4.2 Incidental reverse the course of these ischemic events. Intraventricular or intracerebral bleed 4 2.8 (Symptom totals are greater than patient numbers, since CLINICAL PRESENTATION some patients had multiple symptoms at presentation)

Adult moyamoya patients often present with during follow-up periods of up to 7 years after their hemorrhage, leading to rapid diagnosis. In con- initial arteriogram and surgery, a finding which trast, children usually present with transient is- again indicates how variable a given moyamoya chemic attacks (TIAs) or strokes, which may prove patient's clinical course can be. more difficult to diagnose because of patient's In addition to signs and symptoms, obtaining a inadequate verbal skills, etc., leading to delayed careful history is important in patients suspected recognition of the underlying moyamoyal°. TIAs to have moyamoya. There are a host of prior may be precipitated by events common in children, clinical conditions or syndromes that have been such as hyperventilation with crying; the hyper- associated with moyamoya12. These include prior ventilation can induce cerebral vasoconstriction in radiotherapy to the head or neck for optic gliomas, the cerebral vessels of these patients that have craniopharyngiomas, and pituitary tumors; ge- normal autoregulation and which are maximally netic disorders, such as , neurofi- dilated because of the patient's chronic ischemia. bromatosis type I (NF1) (with or without hypotha- The subsequent constriction of these previously lamic-optic pathway tumors), large facial heman- dilated vessels can in turn cause a significant giomas, sickle cell anemia and other hemoglobin- reduction in the already marginal cerebral perfu- opathies; autoimmune disorders such as Graves' sion in these patients and lead to TIA or stroke. Disease; congenital cardiac disease; renal artery Headache is a common presenting symptom in stenosis; meningeal infections, including tuber- children with moyamoya. Although the etiology is culous ;; and a host of unique syn- unclear, there is speculation that dilatation of dromes such as Williams, Alagille, etc. Table 2 meningeal and leptomeningeal collateral vessels summarizes the clinical associations noted in our may stimulate dural nociceptors. Seizures (both recently published series60. focal and global), focal neurologic deficits, chore- oathetotic movements and hemorrhage are also PATHOLOGY AND ETIOLOGY presenting signs and symptoms of these patients. Table 1 summarizes the clinical presentation in a In moyamoya syndrome, stenosis occurs in the recently published series of 143 patients from our distal intracranial carotid arteries and often in- institution6. Lastly, a rare but reported manifesta- volves the proximal anterior and middle cerebral tion of patients with moyamoya syndrome is non- arteries. Pathologic analysis has demonstrated traumatic acute , which is that affected vessels generally do not exhibit arte- presumed to result from spontaneous rupture of riosclerotic or inflammatory changes. While the transdural collateral vessels". At the time of their etiology of moyamoya remains unknown, several initial presentation, almost ahl children have bilat- investigations have made some inroads towards eral involvement by arteriography. In the senior understanding this disease. Basic fibroblast growth author's personal series, however, 16 patients had factor (13FGF), has been shown to be elevated in purely unilateral angiographic and clinical find- assays of dura and scalp arteries in patients with ings at presentation. Over periods ranging from 6 moyamoya syndrome as well as in the cerebrospi- months to 4 years, 9 of these progressed to develop nal fluid (CSF) of children with moyamoya syn- opposite hemisphere symptoms or had develop- drome, sampled at the time of revascularization ment of significant stenoses in previously normal surgery13-16 Intracellular adhesion molecules are vessels in the opposite hemisphere. Seven patients similarly elevated in the CSF of these patients17. with unilateral disease, however, did not progress These findings suggest that there may be an as yet undefined systemic process underlying the vas-

VOL 19, 2005 MOYAMOYA SYNDROME 33

Table 2. Associated conditions, risk factors, or syndromes

Syndrome

66 No associated conditions (idiopathic) (NF 1) 16

Asian 16

Cranial therapeutic radiation 15 (hypothalamic-optic system glioma 8) (craniopharyngioma 4) (medulloblastoma, with Gorlin's Syndrome 1) (acute lymphocytic leukemia, intrathecal chemotherapy 2)

10 Down syndrome Congenital cardiac anomaly, previously-operated 7

4 Renal artery stenosis 3 Hemoglobinopathy (2 sickle cell, 1 "Bryn Mawr") (Other Hematologic: 1 spherocytosis, 1 ITP) 2

Giant cervico-facial hemangiomas 3

Shunted 3

Idiopathic hypertension requiring medication 3 (one with Graves Syndrome) 2 Other syndromes, 1 patient each: Reyes (remote), Williams, Alagille, cloacal extrophy, renal artery fibromus- cular dysplasia, and congenital cytomegalic inclusion virus infection (remote). Two patients had unclassified syndromic presentations. There were 4 African Americans, 2 of whom had . culopathy in certain patients. Morphometric anal- two sets of identical twins, only one sibling in each yses have demonstrated similar abnormalities in pair having moyamoya syndrome, again suggest- pulmonary, renal, cardiac, and pancreatic arter- ing that some type of environmental factor must ies in certain patients with moyamoya syndrome' 8• precipitate the syndrome's clinical emergence in Moreover, the fact that moyamoya syndrome oc- susceptible patients. Ultimately the pathogenesis curs in patients with congenital cardiac and uro- of moyamoya syndrome may involve both genetic genital anomalies, including patients with Down and environmental factors. syndrome and in patients with renal artery steno- sis, suggests that in these conditions there may be NATURAL HISTORY AND PROGNOSIS a common genetic alteration in the makeup of vascular structures.19 The prognosis of moyamoya syndrome is diffi- Evidence exi'sts supporting the premise that cult to predict because the natural history of this genetic factors are important in the pathogenesis disorder has not yet been elucidated. The progres- of this disorder. A familial incidence in Japan of 7- sion of disease can be slow, with rare, intermittent 12% and a rate of affected first-degree relatives of events, or can be fulminant, with rapid neurologic approximately 6% in the Children's Hospital, Bos- decline12'27. However, regardless of the course, it ton, series substantiate this hypothesis20'21. Ge- seems clear that moyamoya syndrome , both in netic analysis has suggested associations be- terms of arteriopathy and clinical symptoms, in- tween moyamoya patients and abnormalities on evitably progresses in untreated patients4. chromosomes 3, 6 and 1722 23. Hopefully further Overall prognosis of patients with moyamoya study of this disorder will lead to improved under- syndrome depends on the rapidity and extent of standing and, ultimately, better therapy of vascular occlusion, the patient's ability to develop moyamoya syndromes. effective collateral circulation, the age at onset of In addition to genetic factors, it appears that symptoms, the severity of presenting neurological environmental influences contribute to the patho- deficits and degree of disability, and the extent of genesis of moyamoya syndrome. The finding that infarction seen on computed tomography or mag- patients can develop this syndrome in a delayed netic resonance imaging studies at the time of fashion after radiation therapy, or after acquiring initial presentation28. In general, neurologic sta- certain types of infectious illnesses lend credence tus at time of treatment, more so than age of the to the role of non-genetic causes ofmoyamoyal9'24- patient, predicts long term outcome27'29. 26. In the senior author's personal series, there are Importantly, if surgical revascularization is per-

34 E.R. SMITH ET AL REV. ARGENT. NEUROC. formed prior to disabling infarction in moyamoya nostic imaging modality for moyamoya syndrome syndrome, even if severe angiographic changes are instead of conventional cerebral angiography32-38. present, the prognosis tends to be excellent. How- While MRA affords the ability to detect stenosis of ever, if left untreated, both the angiographic pro- the major intracranial vessels, visualization of cess and the clinical syndrome invariably progress, basal moyamoya collateral vessels and smaller producing clinical deterioration with potentially vessel occlusions is frequently subject to artifact. irreversible neurological deficits over time30. Therefore, to confirm the diagnosis of moyamoya syndrome and to visualize the anatomy of the DIAGNOSIS vessels involved and the pattems of flow through the hemispheres, conventional cerebral angiogra- Moyamoya syndrome should be considered phy is typically required. and diagnostic evaluation begun in any child Angiography should consist of a full four ves- who presents with symptoms of cerebral ischemia sel series, including selective injection of the (e.g., a transient ischemic attack manifesting as external carotid systems. The diagnosis of episodes of hemiparesis, speech disturbance, moyamoya is said by the Japanese to require sensory impairment, involuntary movement, and/ bilateral symmetrical stenosis or occlusion of the or visual disturbance), especially if the symp- terminal portion of the intracranial carotid arter- toms are precipitated by physical exertion, hy- ies as well as the presence of dilated collateral perventilation, or crying. The diagnosis of vessels that develop at the base of the brain moyamoya is confirmed by radiographic studies. producing the classic "puff ofsmoke" appearance Signs of moyamoya can be direct, such as the on angiography. External carotid imaging is es- characteristic arterial narrowing and "puff of sential to identify preexisting collateral vessels, smoke" collaterals, or can be indirect, such as so that surgery, if performed, will not disrupt evidence of cerebral hypoperfusion or multiple them. or AVMs, known to be associ- infarcts. Radiographic evaluation of a given pa- ated with some cases of moyamoya, can also be tient suspected of having moyamoya usually best detected by conventional angiography. proceeds through severa! studies. The angiographic appearance of moyamoya has The workup of a patient in whom the diagnosis of been classified into six progressive stages4. The first moyamoya syndrome is suspected typically begins stage is characterized by carotid stenosis without with a head CT scan. Commonly, small areas of collateral vessels. In the second stage, basal collat- hypodensity suggestive of stroke are observed in eral vessels are seen and in the third stage, these cortical watershed zones, basal ganglia, deep white vessels become more prominent, often associated matter or periventricular regions. Although rare in clinically with symptomatic presentation of the pa- children, hemorrhage from moyamoya vessels can be tients. During the fourth stage, the entire circle of readily diagnosed on head CT, with the most common Willis and posterior cerebral arteries become severe- sites of hemorrhage being the basal ganglia, ventric- ly stenotic or completely occluded, moyamoya ves- ular system, medial temporal lobes, and thalamus. sels begin to narrow, and extracranial collateral Patients with these findings on CT are often networks begin to forrn. It is the prominence of these subsequently evaluated with a MR!! MRA. Acute extracranial vessels which is the hallmark of the fifth infarcts are well seen using diffusion weighted stage, and they become the only source of blood imaging (DWI), chronic infarcts are better delin- supply to the brain following complete occlusion of eated with Ti and T2 imaging and cortical is- the carotids in the sixth stage. chemia may be inferred from FLAIR sequences Other diagnostic studies that can assist in the which demonstrate linear high signal following a workup of patients with moyamoya syndrome in- sulcal pattem, felt to represent slow flow in poorly- dude electroencephalography (EEG) and cerebral perfused cortical circulation31. Most suggestive of blood flow studies. Specific alterations of EEG moyamoya on MRI is the finding of diminished recordings are usually observed only in pediatric flow voids in the internal carotid and middle and patients, and include posterior or centrotemporal anterior cerebral arteries coupled with prominent slowing, a hyperventilation-induced diffuse pat- collateral flow voids in the basal ganglia and tern of monophasic slow waves (i. e. , build-up), and thalamus. These imaging findings are virtually a characteristic "rebuild-up" phenomenon39. This diagnostic of moyamoya syndrome. "rebuild-up" phenomenon, which occurs after hy- Because of the excellent diagnostic yield and perventilation and involves the appearance of char- noninvasive nature of MR imaging, it has been acteristic slow waves after disappearance or atten- proposed that MRA be used as the primary diag- uation of initial slowing, is an EEG finding charac-

VOL 19, 2005 MOYAMOYA SYNDROME 35 teristic of moyamoya syndrome and is observed in The antiplatelet effect of aspirin is useful in roughly 50% of children with this disorder. After moyamoya because some ischemic symptoms ap- approximately 10 minutes, the rebuild-up resolves pear to occur as a consequence of emboli from and the EEG pattem retums to baseline. microthrombus formation at sites of arterial stenos- Cerebral blood flow studies, utilizing tech- es12,27,46,47. At The Children's Hospital, Boston, chil- niques such as transcranial Doppler ultrasonog- dren with moyamoya are treated with lifelong aspi- raphy (TCD), xenon-enhanced CT, positron emis- rin therapy, with those less than 6 years of age sion tomography (PET), and single photon emis- receiving 81 mg/day and at a variable dose in older sion computed tomography (SPECT) with aceta- children, depending on the presence or absence of zolamide challenge, also can be helpful in the symptoms. While anticoagulants like warfarin are diagnostic evaluation of patients with moyamoya rarely used due to the difficulty of maintaining syndrome as well as assisting in treatment deci- therapeutic levels in children, we have begun to use sions. For example, transcranial Doppler exam- low dose low-molecular weight heparin (Lovenox) at ination provides a noninvasive way to follow 0.5 mg/kg twice a day subcutaneously for selected changes in blood flow patterns over time in larger children, particularly those children who are neuro- cerebral vessels, while xenon CT, PET, and SPECT logically unstable and need rapidly-reversible anti- can be used both to detect regional perfusion coagulation prior to procedures such as surgery or instability prior to treatment and to determine angiography that preclude aspirin use. In these the extent of improvement of functional perfu- cases, the aspirin is held for ten days prior to the sion after therapy40-45. procedure and the heparin is employed as a "bridge" Although each of these studies has the poten- to provide some protection which has a shorter tial to add information in the diagnosis and man- pharmacologic half-life than aspirin. After the pro- agement of moyamoya, not ahl are routinely used cedure is completed, aspirin is usually restarted. at our institution In our patients, MRI/A and The other medication class that has been useful conventional angiography are the standard diag- in the treatment ofcertain symptoms in moyamoya nostic tools utilized for most patients with syndrome is calcium channel blockers46. These moyamoya; following surgical treatment, an an- drugs may be particularly useful in ameliorating giogram and an MRI/MRA are obtained one year symptoms of intractable or , after operation, and depending on the age of the commonly seen in moyamoya patients, and also patient, subsequent yearly MR imaging. seems to be effective in reducing both the frequency and severity of refractory TIA. TREATMENT CONSIDERATIONS SURGICAL TREATMENT Once a major stroke or hemorrhage has oc- curred, children with moyamoya syndrome fre- There are a number of studies in the literature quently are left with permanent neurologic im- that support a role for surgical management of pairment12'46. Therefore, early diagnosis and moyamoya disease, and surgery is generally rec- prompt treatment of this disorder are of utmost ommended for the treatment of patients with recur- importance in order to prevent additional neuro- rent or progressive cerebral ischemic events and logic deficits. Despite this urgency, there is no associated reduced cerebral perfusion reserve. Many agreed-upon method of treatment for patients different operative techniques have been described, with this chronic occlusive cerebrovascular disor- all with the main goal ofpreventing further ischem- der. There are reports of some patients who stabi- ic injury by increasing collateral blood flow to lize clinically without intervention, but this typi- hypoperfused areas of cortex, using the extemal cally occurs after they have experienced signifi- carotid circulation as a donor supply12,27. cant, debilitating neurologic disability. Various bypass procedures have been performed in the treatment of moyamoya disease, which can MEDICAL TREATMENT generally be divided into direct and indirect types. Direct anastomosis procedures, most commonly Currently, there is no known medical treat- superficial temporal artery (STA) to middle cerebral ment capable of reversing or stabilizing progres- artery (MCA) bypasses, may achieve instant im- sion of moyamoya syndrome. However, there is provement in focal cerebral perfusion, but these support for the use of two classes of medications procedures are often technically difficult to perform to slow the progression of the disease; anticoagu- because small pediatric patients often do not have lants/antiplatelet agents and vasodilators. a large enough donor scalp artery or recipient 36 E.R. SMITH ET AL REV. ARGENT. NEUROC. to allow for a anastomosis ed improved results in the use of combined direct large enough to supply a significant amount of and indirect anastamoses56'57'68. additional collateral blood supply. Because of prox- At The Children's Hospital, Boston, we utilize a imal stenoses, new blood supply provided to a modification of the EDAS procedure to treat single MCA branch may not allow wide redistribu- moyamoya syndrome in both children and adults tion of the newly available collateral. Temporary termed "pial synangiosis," which we believe leads occlusion of a middle cerebral branch during the to a superb induction of new collateral vessels in anastomosis may interfere with leptomeningeal the patient with chronic ischemia due to collateral pathways already present and lead to an moyamoya27. The technique involves the following increased incidence of perioperative stroke. steps: 1) a scalp donor artery (most commonly, the A variety of indirect anastomotic procedures posterior branch of the superficial temporal ar- have been described: encephaloduroarteriosynan- tery) is dissected from distal to proximal along giosis (EDAS) whereby the STA is dissected free with a cuff of galea and surrounding soft tissue; 2) over a course of several inches and then sutured to a large craniotomy is tumed in the region that is the cut edges of the opened dura; encephalomyo- subjacent to the artery; 3) the dura is opened into synangiosis (EMS) in which the temporalis muscle at least six fiaps in order to increase the surface is dissected and placed onto the surface of the brain area of dura exposed to the pial surface and to encourage collateral vessel development; and thereby enhance formation of collateral vessels the combination of both, encephalo-myo-arterio- from the dural vascular supply; 4) the arachnoid synangiosis (EMAS)48-50. There are multiple varia- is opened widely over the surface of brain exposed tions of these procedures, including solely drilling by the dural opening (fig. 1); and 5) the intact burr holes, without vessel anastomosis51'52, and donor artery is sutured directly to the pial surface craniotomy with inversion of the dura in hopes of using four to six interrupted 10-0 nylon sutures enhancing new dural revascularization of the placed through the donor vessel adventitia and brain.53 Cervical sympathectomy and omental the underlying pia (fig. 2, 3). The bone flap is transposition or omental pedicle grafting have also replaced over a gel-foam cover of the dura, which been described54-64. Increased levels of angiogenic is left widely open, and carefully secured to avoid factors, such as bFGF -which has been shown to be compression of the donor artery. The temporal significantly elevated in the of muscle and skin edges are carefully closed with patients with moyamoya syndrome- may contrib- absorbable sutures to similarly avoid compres- ute to the effectiveness of both indirect (i.e., EDAS, sion of the donor vessel. The rationale behind this EMS, pial synangiosis, and burr holes) and direct procedure is that opening the arachnoid removes (i. e . , STA-MCA bypass) revascularization techniques a barrier to the ingrowth of new blood vessels into by enhancing the formation and ingrowth of new the brain from the sources provided to it; the blood vessels from extracranial sources14,16,65. donor vessel's adventitia is sutured to the pial Another variation of indirect revascularization surface to maintain its contact with the brain in is to split the dura to improve collateral develop- ment. At surgery, a portion of the dura near the branches of the middle meningeal artery is split into outer and inner layers, and the split surface of the outer layer is placed on the cortical surface. This procedure, combined with a standard en- cephaloduroarteriosynangiosis, demonstrated ef- fective cortical revascularization through the du- ral arteries as well as from the scalp arteries. A histological study of the dura in cases of moyamoya disease showed an increased number of blood vessels in the outer layer66. The use of a muscle flap to provide revascularization may lead to brain edema due to mass effect from the muscle pedicle itself and one group proposed that following EDAMS with dural pedicle insertion, the bone flap be shaved to half of its original thickness, that the patient be routinely placed on mannitol postoper- Fig. 1. Photomicrographillustrating opening of the arach- atively67. Finally, a number of groups have report- noid over a cortical vessel using line forceps.

VOL 19, 2005 MOYAMOYA SYNDROME 37

ative EEG or near-infrared spectroscopy, used to identify and ameliorate ischemic events detected while the patient is under general anesthesia70'71. At our institution, we have been using full scalp EEG monitoring during procedures where both hemisphere will be operated on during the same anesthetic. It has helped us identify situations in which continuing with the second side was felt to be unsafe for the patient, but its definitive role is yet to be established, and many EEG changes are observed throughout the procedures that are difficult to interpret. We have noted that the addition of thrombin to our gelfoam pledget cov- ering the brain at the time of closure is associated with almost invariable EEG slowing, and we have since omitted the use of thrombin at this stage of Fig. 2. Photomicrographilhistrating suture (10-0 nylon) pas- the operation with a marked reduction in the sed through adventitia of donor vessel prior to pial stitch. occurrence of this phenomenon. Postoperative angiograms are usually obtained twelve months after surgery and typically demon- strate excellent MCA collateralization from both the donor STA and the meningeal arteries. A review of one hundred and forty-three children with moyamoya syndrome treated with pial synan- giosis had marked reductions in their stroke fre- quency after surgery, especially after the first year postoperatively. In this group, 67% had strokes preoperatively, 7.7% had strokes in the perioper- ative 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-up27. This work supports the premise that pial synangiosis provides a signifi- Fig. 3. Photograph of donor artery after pial synangiosis cant protective effect against new strokes in this demonstrating attachment to cortical surface and wide patient population. arachnoidal opening. PERIOPERATIVE AND INTRAOPERATIVE arcas where the arachnoid has been cleared. CONSIDERATIONS IN THE SURGICAL MAN- Once the decision for surgical therapy has AGEMENT OF PATIENTS WITH MOYAMOYA been made, several perioperative considerations SYNDROME need to be addressed. In addition to the general issues regarding surgery in children, moyamoya Risks of surgery are more often related to patients are at particular risk of ischemic events neurologic instability of the patient at the time of in the perioperative period. Crying and hyperven- surgery and to the risks of anesthesia rather than tilation, common occurrences in children at times to actual surgical manipulations. The administra- during hospitalization, can lower pCO2 and in- tion of general anesthesia can result in transient, duce ischemia secondary to cerebral vasocon- but significant, physiologic changes which can striction. Any techniques to reduce pain -includ- affect cerebral blood flow. Blood pressure, blood ing the use of perioperative sedation, painless volume and PaCO2 require careful monitoring wound dressing techniques, and absorbable because moyamoya patients have a diminished wound suture closures- helped to reduce the cerebral perfusion reserve and deviation from incidence of strokes, TIAs and length of stay in a normal levels can result in stroke. recent study69. A further perioperative consider- To reduce the risk of intraoperative and perio- ation is the use of monitoring, such as intraoper- perative neurologic morbidity, therefore, meticu-

38 E.R. SMITH ET AL REV. ARGENT. NEUROC.

bus management of the patient is required to view. Stroke 1983; 14: 104-9. avoid hypotension, hypovolemia, hyperthermia, 6. Caldarelli M, Di Rocco C, Gaglini P. Surgical treat- and hypocarbia both intraoperatively as well as ment of moyamoya disease in pediatric age. J perioperatively27. As noted aboye, intraoperative Neurosurg Sci 2001; 45: 83-91. 7. EEG monitoring with a full array of scalp elec- Yonekawa Y, Ogata N, Kaku Y, Taub E, Imhof HG. Moyamoya disease in Europe, past and present trodes can be helpful in the neurologic assess- status. Clin Neurol Neurosurg 1997; 99 Suppl 2: ment of patients under general anesthesia. To S58-60. help prevent hypovolemia during surgery, we ad- 8. Han DH, Kwon OK, Byun BJ, Choi BY, Choi CW, mit patients the evening prior to surgery for ag- Choi JU et al. A co-operative study: clinical charac- gressive intravenous hydration. Postoperatively, teristics of 334 Korean patients with moyamoya the patients are hydrated with intravenous fluids disease treated at neurosurgical institutes (1976- at one and one-half the normal maintenance rate 1994). Acta Neurochir (Wien) 2000; 142: 1263-73. 9. Yilmaz EY, Pritz MB, Bruno A, Lopez-Yunez A, based on weight for 48-72 hours. Aspirin is given Biller J. Moyamoya: Indiana University Medical on the first postoperative day. Center experience. Arch Neurol 2001; 58: 1274-8. Potential complications associated with surgi- 10. Nishimoto A UK, Onbe H. Cooperative study on cal treatment of moyamoya syndrome include moyamoya disease in Japan, 1981; 53-8. postoperative stroke, subdural hematoma, both 11. Nakakita K, Tanaka S, Fukuda A, Fujii C, Kohama following trauma and spontaneous, and intrace- A, Miyasato H. [Nontraumatic acute subdural he- rebral hemorrhage. Although wound infection and matoma caused by the rupture of transdural anas- CSF leak can occur after any cranial procedure, tomotic vessels in moyamoya disease]. No Shinkei we have only one such a complication in our pial Geka 1994; 22: 1-565. synangiosis series which now numbers over 200 12. Ohaegbulam C MS, Scott RM. Moyamoya syn- drome. In: McLone D, ed. Pediatric Neurosurgery. pediatric patients - despite the fact that the dura Philadelphia: WB Saunders; 2001: 77-1092. is left widely open following the synangiosis. 13. Hoshimaru M, Takahashi JA, Kikuchi H, Nagata I, Hatanaka M. Possible roles of basic fibroblast CONCLUSIONS growth factor in the pathogenesis of moyamoya disease: an immunohistochemical study. J Neuro- Moyamoya syndrome is an increasingly recog- surg 1991; 75: 267-70. nized entity which is associated with cerebral 14. Takahashi A, Sawamura Y, Houkin K, Kamiyama ischemia. Diagnosis is made on the basis of clin- H, Abe H. The cerebrospinal fluid in patients with ical and radiographic findings, including a char- moyamoya disease (spontaneous occlusion of the circle of Willis) contains high level of basic fibro- acteristic stenosis of the internal carotid arteries blast growth factor. Neurosci Lett 1993; 160: 214- in conjunction with abundant collateral vessel 6. development. Treatment is predicated on revascu- 15. Suzui H, Hoshimaru M, Takahashi JA, etal. Immu- larization of the ischemic brain, which can be nohistochemical reactions for fibroblast growth direct (STA-MCA bypass) or indirect (including factor receptor in arteries of patients with moyamoya pial synangiosis). The use of pial synangiosis is a disease. Neurosurgery 1994; 35: 20-4; discussion safe, effective and durable method of cerebral 24-5. revascularization in moyamoya syndrome and 16. Malek AM, Connors S, Robertson RL, Folkman J, should be considered as a primary treatment for Scott RM. Elevation of cerebrospinal fluid levels of basic fibroblast growth factor in moyamoya and moyamoya, especially in the pediatric population. central disorders. Pediatr Neuro- surg 1997; 27: 182-9. Bibliography 17. Soriano SG, Cowan DB, Proctor MR, Scott RM. Levels of soluble adhesion molecules are elevated 1. Nagaraj a D, Verma A, Taly AB, Kumar MV, Jayaku- in the cerebrospinal fluid of children with moyamoya mar PN. in children. Acta syndrome. Neurosurgery 2002; 50: 544-9. Neurol Scand 1994; 90: 251-5. 18. Ikeda E. Systemic vascular changes in spontane- 2. Soriano SG, Sethna NF, Scott RM. Anesthetic ous occlusion of the circle of Willis. Stroke management of children with moyamoya syndrome. 1991;22:1358-62. Anesth Analg 1993; 77: 1066-70. 19. Gordon N, Isler W. Childhood moyamoya disease. 3. K. TKS. Hypoplasia of the bilateral interna! carotid Dev Med Child Neurol 1989; 31: 103-7. arteries. Brain Nerve 1957; 9: 37-43. 20. Kitahara T, Ariga N, Yamaura A, Makino H, Maki Y. 4. Suzuki J TA. Cerebrovascular "moyamoya" dis- Familial occurrence of moya-moya disease: report ease: Disease showing abnormal net-like vessels in of three Japanese families. J Neurol Neurosurg base of brain. Arch Neurol 1969; 20: 288-99. Psychiatry 1979; 42: 208-14. 5. Suzuki J, Kodama N. Moyamoya disease-a re- 21. Sogaard I, Jorgensen J. Familial occurrence of

VOL 19, 2005 MOYAMOYA SYNDROME 39

bilateral intracranial occlusion of the intemal ca- maximum intensity projection in patients with rotid arteries (Moya Moya). Acta Neurochir (Wien) childhood moyamoya disease. Eur J Paediatr Neu- 1975; 31: 245-52. rol 1998; 2: 83-9. 22. Yamauchi T, Tada M, Houkin K, Tanaka T, Naka- 38. Chang KH, Yi JG, Han MH, Kim JO. MR imaging mura Y, Kurada S. et al. Linkage of familial findings of moyamoya disease. J Korean Med Sci moyamoya disease (spontaneous occlusion of the 1990; 5: 85-90. circle of Willis) to chromosome 17q25. Stroke 39. Kodama N, Aoki Y, Hiraga H, Wada T, Suzuki J. 2000; 31: 930-5. Electroencephalographic findings in children with 23. Inoue TK, Ikezaki K, Sasazuki T, Matsushima T, moyamoya disease. Arch Neurol 1979; 36: 16-9. Fukui M. Linkage analysis of moyamoya disease on 40. Takase K, Kashihara M, Hashimoto T. Transcrani- chromosome 6. J Child Neurol 2000; 15: 79-182. al Doppler ultrasonography in patients with 24. Kestle JR, Hoffman HJ, Mock AR. Moyamoya phe- moyamoya disease. Clin Neurol Neurosurg 1997; nomenon after radiation for optic glioma. J Neuro- 99 Suppl 2: S101-5. surg 1993; 79: 32-5. 41. Morgenstem C, Griewing B, Muller-Esch G, Zeller 25. Okuno T, Prensky AL, Gado M. The moyamoya JA, Kessler C. Transcranial power-mode duplex syndrome associated with irradiation of an optic ultrasound in two patients with moyamoya syn- glioma in children: report of two cases and review drome. J Neuroimaging 1997; 7: 190-2. of the literature. Pediatr Neurol 1985; 1: 311-6. 42. Takeuchi S, Tanaka R, Ishii R, Tsuchida T, Koba- 26. Bitzer M, Topka H. Progressive cerebral occlusive yashi K, Arai H. Cerebral hemodynamics in pa- disease after radiation therapy. Stroke 1995; 26: tients with moyamoya disease. A study of regional 131-6. cerebral blood flow by the 133Xe inhalation meth- 27. Scott RM, Smith JL, Robertson RL, Madsen JR, od. Surg Neurol 1985; 23: 468-74. Soriano SG, Rockoff MA. Long-term outcome in 43. Nambu K, Suzuki R, Hirakawa K. Cerebral blood children with moyamoya syndrome after cranial flow: measurement with xenon-enhanced dynamic revascularization by pial synangiosis. J Neurosurg helical CT. Radiology 1995; 195: 53-7. 2004; 100: 142-9. 44. Liu HM, Peng SS, Li YW. The preoperative and 28. Maki Y, Enomoto T. Moyamoya disease. Childs postoperative cerebral blood flow and vasoreactiv- Nerv Syst 1988; 4: 204-12. ity in childhood moyamoya disease. Keio J Med 29. Fukuyama Y, Umezu R. Clinical and cerebral an- 2000; 49 Suppl 1: A86-9. giographic evolutions of idiopathic progressive oc- 45. Shirane R, Yoshida Y, Takahashi T, Yoshimoto T. clusive disease of the circle of Willis ("moyamoya" Assessment of encephalo-galeo-myo-synangiosis disease) in children. Brain Dev 1985; 7: 21-37. with dural pedicle insertion in childhood moyamoya 30. Imaizumi T, Hayashi K, Saito K, Osawa M, Fuku- disease: characteristics of cerebral blood flow and yama Y. Long-term outcomes ofpediatric moyamoya oxygen metabolism. Clin Neurol Neurosurg 1997; disease monitored to adulthood. Pediatr Neurol 99 Suppl 2: S79-85. 1998; 18: 321-5. 46. Scott RM. Moyamoya syndrome: a surgically treat- 31. Chabbert V, Ranjeva JP, Sevely A, Boetto S, Berry able cause of stroke in the pediatric patient. Clin I, Manelfe C. Diffusion- and magnetisation trans- Neurosurg 2000; 47: 378-84. fer-weighted MRI in childhood moya-moya. Neuro- 47. Scott RM. Surgery for moyamoya syndrome? Yes. radiology 1998; 40: 267-71. Arch Neurol 2001; 58: 128-9. 32. Yamada I, Suzuki S, Matsushima Y. Moyamoya 48. Matsushima T, Inoue T, Katsuta T, Natori Y, Suzu- disease: comparison of assessment with MR an- ki S, Ikesaki K et al. An indirect revascularization giography and MR imaging versus conventional method in the surgical treatment of moyamoya angiography. Radiology 1995; 196: 211-8. disease. Neurol Med Chir (Tokyo) 1998; 38 Suppl: 33. Yamada I, Matsushima Y, Suzuki S. Childhood S297-302. moyamoya disease before and after encephalo- 49. Kawaguchi S, Okuno S, Sakaki T. Effect of direct duro-arterio-synangiosis: an angiographic study. arterial bypass on the prevention offuture stroke in Neuroradiology 1992; 34: 318-22. patients with the hemorrhagic variety of moyamoya 34. Yamada I, Matsushima Y, Suzuki S. Moyamoya disease. J Neurosurg 2000; 93: 397-401. disease: diagnosis with three-dimensional time-of- 50. Houkin K, Kamiyama H, Abe H, Takahashi A, flight MR angiography. Radiology 1992; 184: 773- Kuroda S. Surgical therapy for adult moyamoya 8. disease. Can surgical revascularization prevent 35. Yamada I, Suzuki S, Matsushima Y. Moyamoya the recurrence ofintracerebral hemorrhage? Stroke disease: diagnostic accuracy of MRI. Neuroradiol- 1996; 27: 1342-6. ogy 1995; 37: 356-61. 51. Sencer S, Poyanli A, Kiris T, Sencer A, Minareci O. 36. Katz DA, Marks MP, Napel SA, Bracci PM, Roberts Recent experience with Moyamoya disease in Tur- SL. Circle of Willis: evaluation with spiral CT an- key. Eur Radiol 2000; 10: 569-72. giography, MR angiography, and conventional an- 52. Houkin K, Kuroda S, Nakayama N. Cerebral revas- giography. Radiology 1995; 195: 445-9. cularization for moyamoya disease in children. 37. Takanashi JI, Sugita K, Niimi H. Evaluation of Neurosurg Clin N Am 2001; 12: 575-84. magnetic resonance angiography with selective 53. Dauser RC, Tuite GF, McCluggage CW. Dural 40 E.R. SMITH ET AL REV. ARGENT. NEUROC.

inversion procedure for moyamoya disease. Tech- cerebrovascular moyamoya disease: a two-year nical note. J Neurosurg 1997; 86: 719-23. follow-up study. Surg Neurol 1980; 14: 444-9. 54. Sato H, Ogawa A, Takahashi A, Fujiwara S, Saku- 62. Karasawa J, Touho H, Ohnishi H, Miyamoto S, rai Y, Kayama T et al. [Influence of superior cervical Kikuchi H. Cerebral revascularization using ornen- ganglion on cerebral hemodynamics-measure- tal transplantation for childhood moyamoya dis- ments of cerebral blood flow and metabolism dur- case. J Neurosurg 1993; 79: 192-6. ing superior cervical ganglionectomy in patients 63. Havlik RJ, Fried I, Chyatte D, Modlin IM. Enceph- with moyamoya disease]. No To Shinkei. 1990; 42: alo-omental synangiosis in the management of 203-8. moyamoya disease. Surgery 1992; 111: 156-62. 55. Ohtaki M, Uede T, Morimoto S, Nonaka T, Tanabe 64. Suzuki J, Takaku A, Kodama N, Sato S. An attempt S, Hashi K. Intellectual functions and regional to treat cerebrovascular `Moyamoya' disease in cerebral haemodynamics after extensive omental children. Childs Brain 1975; 1: 193-206. transplantation spread over both frontal lobes in 65. Mizoi K, Kayama T, Yoshimoto T, Nagamine Y. childhood moyamoya disease. Acta Neurochir Indirect revascularization for moyamoya disease: (Wien) 1998; 140: 1043-53. is there a beneficial effect for adult patients? Surg 56. Matsushima T, Inoue T, Ikezaki K, Matsukado K, Neurol 1996; 45: 541-8; discussion 548-9. Natori Y, Inamura T, Fukui M. Multiple combined 66. Kashiwagi S, Kato S, Yasuhara S, Wakuta Y, Ya- indirect procedure for the surgical treatment of mashita T, Ito H. Use of a split dura for revascular- children with moyamoya disease. A comparison ization of ischemic hemispheres in moyamoya dis- with single indirect anastomosis with direct anas- case. J Neurosurg 1996; 85: 380-3. tomosis. Neurosurgical Focus 1998; 5: Article 4. 67. Takemura S, Sato S, Kuroki A, Saito S, Kayama T. 57. Matsushima Y. [Indirect anastomoses for moyamoya [New ideas for indirect revascularization surgery disease]. No Shinkei Geka. 1998; 26: 769-86. for moyamoya disease]. No Shinkei Geka. 1999; 58. Yoshioka N, Tominaga S, Inui T. Cerebral revascu- 27: 987-92. larization using omentum and serratus anterior 68. Ikezaki K. Rational approach to treatment of muscle free flap transfer for adult moyamoya dis- moyamoya disease in childhood. J Child Neurol case: case report. Surg Neurol 1996; 46: 430-5. 2000; 15: 350-6. 59. Yoshioka N, Tominaga S, Suzuki Y, et al. Cerebral 69. Nomura S, Kashiwagi S, Uetsuka S, Uchida T, revascularization using omentum and muscle free Kubota H, Ito H. Perioperative management proto- flap for ischemic cerebrovascular disease. Surg cols for children with moyamoya disease. Childs Neurol 1998; 49: 58-65; discussion 65-6. Nerv Syst 2001; 17: 270-4. 60. Touho H, Karasawa J, Tenjin H, Ueda S. Omental 70. Lin Y, Yoshiko K, Negoro T, Watanabe K, Negoro M. transplantation using a superficial temporal artery Cerebral oxygenation state in childhood moyamoya previously used for encephaloduroarteriosynangi- disease: a near-infrared spectroscopy study. Pedi- osis. Surg Neurol 1996; 45: 550-8; discussion atr Neurol 2000; 22: 365-9. 558-9. 71. Fujiwara J, Nakahara S, Enomoto T, Nakata Y, administration for 61. Karasawa J, Kikuchi H, Kawamura J, Sakai T. Takita H. The effectiveness of 02 Intracranial transplantation of the omentum for transient ischemic attacks in moyamoya disease in children. Childs Nerv Syst 1996; 12: 69-75.

ABSTRACT

Moyamoya syndrome, a vasculopathy ch.aracterized by symptoms, inevitably progresses in untreated patients. chronic progressive stenosis at the apices of the intracra- Sw-gery is generally recommen.ded for the treatment of nial internal carotid arteries, is a.n increasingly recogni- patients with recurrent or progressive cerebral ischemic zed entity which is associated with cerebral ischemia. events and associated red uced cerebral perfusion reserve. Diagnosis is made on the basis of clinical and radiogra- Many different operative techniques have been des- phic findings, including a characteristic stenosis of the cribed, all with the main goal of preventing further internal carotid arteries in cordunction with a.bundant ischemic injury by increasing collateral blood flow to collateral vessel development. Adult moyamoya pa- hypoperfused areas of cortex, using the external carotid tients often present with hemorrhage, leading to rapid. circulation as a donor supply. This chapter discusses the diagnosis. In contrast, children usually present with various treatment approaches, with an emphasis on the transient ischemic attacks (TIAs) or strokes, which may use of pial synangiosis, a method of indirect revascula- prove more difficult to diagnose because of patient's rization. The use of pial synangiosis is a safe, effective ina.dequate verbal skills, etc., leading to delayed recog- and durable method of cerebral revascularization in nition of the underlying moyamoya. The progression of moyamoya syndrome and should be considered as a disease can be slow, with rare, intermittent events, or primary treatment for moyamoya, especially in the pe- can be fulminant, with rapid neurologic decline. Howe- diatric popula.tion. ver, regardless of the course, it is apparent that moyamo- Key words: arteriopathy, cerebral revascularization, ya syndrome, both in terms of arteriopathy and clinical moyamoya, stroke.