Moyamoya Diseasev2.practicalneurology.com/pdfs/PN0120_CF4_Moyamoya.pdf · 2020-01-08 · a collateral vascular network of small vessels arising from the carotid artery, leptomeninges,

52 PRACTICAL NEUROLOGY JANUARY 2020

U N U S UA L C AU S E S O F S T R O K E

Moyamoya disease is a cerebro-vascular condition characterized by idiopathic chronic progres-sive steno-occlusive changes of the terminal portions and proximal branches of the inter-

nal carotid arteries (ICAs). These changes reduce blood flow through the anterior circulation of the brain causing pro-gressive cerebral ischemia. To compensate for the ischemia, a collateral vascular network of small vessels arising from the carotid artery, leptomeninges, and transdural branches of the external carotid artery (ECA) may form. In the final stag-es of the disease, the brain’s blood supply is provided almost exclusively by the ECA and the vertebrobasilar systems.1,2

Although moyamoya disease was first described in 1957 by Takeuchi and Shimizu3 as “hypoplasia of the bilateral internal carotid artery”, the term moyamoya (a Japanese word that means puff of smoke) was coined 12 years later (1969) by Suzuki and Takaku.4 The puff of smoke is a description of the hazy appearance of the collateral vasculature on angiography. Recently, it has become increasingly apparent that the term moyamoya encompasses many different arteriopathies with distinct genetic and environmental drivers that share a com-mon end-stage radiographic appearance.

Moyamoya TerminologyDisease Vs Syndrome

By definition, people with moyamoya disease typically have the pathognomonic arteriographic findings bilaterally with no associated risk factors. In contrast, people with the characteristic moyamoya vasculopathy who also have cer-tain associated conditions (Box 1) are categorized as having moyamoya syndrome. Those with unilateral arteriographic findings are also said to have moyamoya syndrome, even if they have no other associated risk factor. However, approxi-mately 40% of people who initially present with unilateral moyamoya syndrome eventually develop contralateral vasculopathy, such that they will meet the definition of moyamoya disease if they do not have associated condi-

tions.5 When the term moyamoya is used alone without the distinguishing modifiers syndrome or disease, it refers merely to the findings on cerebral arteriography, regardless of the etiology and/or the laterality.

Atypical MoyamoyaThis term is used by some to describe the pathognomonic

moyamoya arteriography findings in the setting of associ-ated aneurysms or pseudoaneurysms; or in the rare occasion of noncarotid steno-occlusive disease, namely the basilar artery and posterior cerebral arteries.1

Demographic CharacteristicsIncidence

The incidence of moyamoya disease varies geographically, with the highest incidence in eastern Asia. In Japan, the inci-

Moyamoya DiseaseBy Alaa Montaser, MD, PhD and Edward R. Smith, MD

Asian ancestry

Down syndrome

Sickle cell disease

Autoimmune disease (DM I, thyroid disease)

Neurofibromatosis type I (NF1)

Cranial radiation

Congenital structural cardiac disease

Microcephalic osteodysplastic primordial dwarfism (MOPD)

Posterior fossa malformations–hemangiomas–arterial anom-alies–cardiac (PHACE) syndrome defects–eye abnormalities–sternal cleft and supraumbilical raphe syndrome)

Robinow syndrome

Alagille syndrome

Seckel syndrome

Box 1. Conditions Associated With Moyamoya Syndrome

JANUARY 2020 PRACTICAL NEUROLOGY 53


dence of moyamoya is 0.35 per 100,000 people. Moyamoya disease is the most common cerebrovascular disease in children in Japan, with a prevalence of approximately 3 cases per 100,000 children. Many cases in children are consid-ered secondary to a common genetic driver, mutations in the RNF213 gene. Moyamoya disease is uncommon in the nonAsian population with an incidence of 0.086 per 100,000 people in the US, although that number may underrepre-sent the total cases of arteriopathy, including people with sickle cell disease and other cohorts outside of those with Asian ancestry. The incidence in European populations is estimated to be about 10% of that observed in Japan.2

Age and SexMoyamoya disease can occur at any age, however, the

age of presentation follows a bimodal distribution. There is a peak in the first decade of childhood, especially around age 5 years; the second peak is in adulthood around the middle of the fifth decade. Moyamoya disease is more common in women with a 2:1 ratio of women to men in most populations.1

Ethnicity Although moyamoya was originally described as pre-

dominantly affecting populations with Asian ancestry, it has been identified worldwide, in people of varied ethnic back-grounds, including American and European populations. The reported ethnicity-specific incidence rate ratio compared with Caucasian US populations was 4.6 (95% CI, 3.4-6.3) for Asian Americans, 2.2 (95% CI, 1.3-2.4) for African Americans, and 0.5 (95% CI, 0.3-0.8) for Hispanics.6 A family history was present in 10% to 15% of people from Japan with moyamoya and in 3% to 6% of people from western countries.2 In a large North American series, familial moyamoya was reported to account for 3.4% of cases.7 Indeed, the ethnicity pattern and familial penetration suggest that genetic predisposition plays a major role in moyamoya disease.

Natural History and PrognosisThe natural history of moyamoya is variable; however, moy-

amoya progresses in the majority of cases. Progression may have a slow indolent course, an intermittent pattern with rare events, or be fulminant with steep neurologic decline.

It is estimated that up to two-thirds of people with moya-moya disease have symptomatic progression that cannot be halted by medical treatment alone. A large meta-analysis of 1,156 people with moyamoya showed 87% who underwent surgical revascularization (see Surgical Management) had symptomatic benefit in the form of reduction or complete disappearance of symptomatic cerebral ischemia.8,9

The initial neurologic status of an individual is the best predictor of the disease course. Early diagnosis coupled with

close follow-up and intervention when appropriate are the major determinants of a favorable long-term outcome.10

Clinical PresentationThe clinical presentations of moyamoya are attributed to

the changes in intracranial blood flow dynamics and cerebral perfusion. Symptoms can be classified as arising from brain ischemia (eg, strokes, transient ischemic attacks [TIA], and seizures) or as sequelae of the compensatory mechanisms in response to ischemia (eg, hemorrhages from rupture of frag-ile collateral vessels and headaches from dilated collaterals).

Age-Related and Geographic Differences In all age groups, ischemia (TIA or stroke) is the most

common presentation of moyamoya, but adults are 7 times more likely than children to present with intracranial hem-orrhage. Manifestations also vary geographically. In the US, ischemic symptoms are the predominant presentation in adults and children, although adults are still 7 times more likely to have intracranial hemorrhage than children (20% vs 2.8%). In contrast, the rate of adults in Asian populations presenting with hemorrhage (42%) is much higher than among those of Asian descent living in the US.10

Ischemic SymptomsSymptoms are typically dependent on which brain region

is ischemic (eg, frontal, parietal, temporal lobes). Common symptoms include hemiparesis, aphasia, cognitive impair-ment, seizures, syncope, and visual deficits. Ischemic symp-toms may be transient (TIA) or permanent (stroke), and are commonly precipitated in children by hyperventilation (eg, crying, exercise), dehydration, or exertion.

Intracranial HemorrhageClinical symptoms vary according to the location of the

hemorrhage, which can be intraventricular, intraparenchy-mal, or subarachnoid. Hemorrhage has been attributed to rupture of fragile collateral vessels and may also be caused by moyamoya-associated microaneurysms in some cases.1,2

Other Symptoms and SignsHeadache is a frequent presenting symptom and is typically

of a migraine-like quality and refractory to medical treatment. Headache is generally believed to be caused by dilatation of the collateral vessels that may stimulate the dural nociceptors.

Choreiform movement is another presenting symptom of moyamoya in children, attributed to dilated collateral vessels in the basal ganglia.1 Additionally, the morning glory disk is an ophthalmologic finding occasionally seen in moy-amoya. It is highly recommended to obtain cerebrovascular imaging to evaluate for moyamoya if this sign is observed on an ophthalmologic examination.11



EvaluationIn cerebral ischemia, moyamoya should be included in

the differential diagnosis, especially in children, because moya-moya is associated with approximately 6% to 10% of nonperinatal pediatric strokes and TIA.1 Evaluation should consist of clinical assessment, including consideration of specific populations with increased moyamoya risk, and radiographic studies, incorporating MRI and potential digi-tal subtraction angiography (DSA). If moyamoya is identi-fied, careful review of family medical histories is warranted to assess familial moyamoya risk factors, with subsequent referral for genetic counseling if present.

Clinical EvaluationMoyamoya arteriopathy has been reported in association

with a wide range of distinct populations, clinical conditions, and genetic disorders. Awareness of these associations is crucial for the physician to consider moyamoya as a diagnos-tic possibility during the initial evaluation. This is especially important in those who have confounding diagnoses (eg, children with Down syndrome who have a structural cardiac disease as a potential cause of stroke) or who are at high risk of recurrent stroke if not identified in a timely fashion.12

Although most pediatric moyamoya cases are idiopathic, there are population-based patterns. Historically, Asian ancestry is an increased risk factor for moyamoya, with up to 56% of Asian-Americans with moyamoya harboring a spe-cific mutation of RNF213.13 In contrast, only 3.6% to 29% of non-Asian individuals with moyamoya harbor RNF213 muta-tions.13 Additionally, Caucasians with moyamoya in the US have a higher rate of autoimmune disorders, including type I diabetes (8.5% vs 0.4% in the general population) and thy-roid disease (17% vs 8%).14 Down syndrome (with a 26-fold increased likelihood of moyamoya), neurofibromatosis type I (with a 2%-5% prevalence of moyamoya), sickle cell disease, and other associated conditions are summarized in Box 1.1,2

Radiographic StudiesMRI is the current standard for evaluation of cerebral

ischemia (Figure 1). Although protocols may be institution specific, commonly available MRI sequences are generally used, including axial T1-/T2-weighted images to assess struc-tural anatomy and chronic stroke, diffusion-weighted imaging (DWI) and apparent diffusion coefficient values (ADC map) to assess acute stroke, fluid-attenuated inversion recovery (FLAIR) images to assess chronic stroke burden and areas of slow flow (ie, the ivy sign, present in nearly 80% of cases) and MR angiography (MRA) to visualize the circle of Willis.15 Advances in vessel wall imaging may help to differentiate between vasculitis and moyamoya.

If moyamoya is identified on MRI, DSA should be consid-ered, as this modality has increased diagnostic sensitivity for

Figure 1. Radiographic imaging modalities for diagnosis and follow-up of moyamoya include magnetic resonance angiogram (MRA) coronal view (A) demonstrating bilateral stenosis and occlusion (white arrows) of

the internal carotid artery (ICA) terminus, M1 segment of middle cerebral artery (MCA), and A1 segment of anterior cerebral artery (ACA). Notice extensive proliferative changes of the lenticulostriate arteries bilaterally

(red arrows). Axial brain MRI T2WI, at level of basal cisterns (B) and basal ganglia (C) demonstrate void signals (red arrows) of moyamoya collaterals. Axial brain MRI FLAIR sequence (D), showing ivy sign bilaterally (yellow

arrows). Anteroposterior (E) and lateral (F) digital subtraction angiogram (DSA) of the left ICA show stenosis of the terminal ICA and thread-like appearance of the M1 and A1 segments, with reconstitution of MCA and

ACA candelabra by lenticulostriate collaterals; most consistent with Suzuki stage III. Anteroposterior (G) and lateral (H) DSA of the left external carotid artery (ECA) shows intrinsic ECA to ICA transdural collaterals from middle

meningeal and superficial temporal artery. Atypical moyamoya with pos terior cerebral disease (I-L): preoperative (I) and postoperative (J) FLAIR sequence showing preoperative ivy sign and its disappearance following

pial synangiosis (white arrows). Preoperative lateral DSA of left ECA (K) and postoperative lateral DSA of left occipital artery (L) following pial synagniosis using the occipital artery as a donor, demonstrating ingrowth of

collaterals from the occipital artery. Notice the increased size of the donor artery (green arrows) compared to the preoperative DSA.



Figure 1. Radiographic imaging modalities for diagnosis and follow-up of moyamoya include magnetic resonance angiogram (MRA) coronal view (A) demonstrating bilateral stenosis and occlusion (white arrows) of

the internal carotid artery (ICA) terminus, M1 segment of middle cerebral artery (MCA), and A1 segment of anterior cerebral artery (ACA). Notice extensive proliferative changes of the lenticulostriate arteries bilaterally

(red arrows). Axial brain MRI T2WI, at level of basal cisterns (B) and basal ganglia (C) demonstrate void signals (red arrows) of moyamoya collaterals. Axial brain MRI FLAIR sequence (D), showing ivy sign bilaterally (yellow

arrows). Anteroposterior (E) and lateral (F) digital subtraction angiogram (DSA) of the left ICA show stenosis of the terminal ICA and thread-like appearance of the M1 and A1 segments, with reconstitution of MCA and

ACA candelabra by lenticulostriate collaterals; most consistent with Suzuki stage III. Anteroposterior (G) and lateral (H) DSA of the left external carotid artery (ECA) shows intrinsic ECA to ICA transdural collaterals from middle

meningeal and superficial temporal artery. Atypical moyamoya with pos terior cerebral disease (I-L): preoperative (I) and postoperative (J) FLAIR sequence showing preoperative ivy sign and its disappearance following

pial synangiosis (white arrows). Preoperative lateral DSA of left ECA (K) and postoperative lateral DSA of left occipital artery (L) following pial synagniosis using the occipital artery as a donor, demonstrating ingrowth of

collaterals from the occipital artery. Notice the increased size of the donor artery (green arrows) compared to the preoperative DSA.



moyamoya compared with MRI (including the ability to bet-ter differentiate vasculitis) and offers valuable data pertinent to preoperative planning. Transdural collaterals visuallzed on DSA are critical biomarkers of disease that can assess angio-genic potential, predict 1-year postoperative radiographic outcomes and, when incorporated into surgical planning, have been demonstrated to reduce perioperative stroke complications by more than 40%, especially in the setting of previous cranial surgery or shunting.3,16,17 The risk of angio-gram is generally low, with an approximately 1% complica-tion rate at high volume centers.18 Contraindications include contrast allergies, aortic stenosis, and unstable general medi-cal conditions that preclude sedation or anesthesia.

Screening and Genetic TestingWhen moyamoya is diagnosed in a child, families are

frequently concerned about the need to screen other siblings and relatives. Initial screening commonly includes an MRI and MRA, looking for the defining radiographic characteristics of moyamoya.15 Indications for radio-graphic screening are still to be defined, but because the rate of familial involvement is low (3.4% in a large North American series), initial screening of unaffected family members is generally reserved for first-degree relatives of those who have other first- or second-degree relatives with 1) established moyamoya diagnosis, 2) clinical his-tories strongly suggestive of moyamoya (eg, TIA, stroke, severe headaches or seizures without identified cause), or 3) identical twins.7 If an initial screening MRI is normal, it remains unclear what, if any, interval for follow-up imag-ing is appropriate. There is data, however, to indicate that previously normal scans can later evidence clear (and clinically symptomatic) moyamoya, suggesting that follow up may have utility.19

Genetic testing and counseling are also relevant to chil-dren and families diagnosed with moyamoya. There is gen-erally high penetrance of the phenotype with most muta-tions and there is a potential surgical treatment if identi-fied. In North America, only a small minority of pediatric moyamoya cases (<5%) appear to have clear associations with specific mutations, unless the children have Asian heritage (for whom RNF213 mutations exist in 30%-50%). When present, RNF213 mutation with moyamoya has marked significance for familial screening, as data suggest that familial penetrance is approximately 23%. If an indi-vidual carries the mutation, there is a near 50% likelihood of manifesting arteriopathy. Other mutations are rarer, but may be detected by specific clinical or radiographic phe-notypes (ACTA2 carriers with distinctive stellate arteries branching from a dilated proximal internal carotid, GUCY mutations with achalasia, etc.).7,13 Current moyamoya-associated mutations are noted in Box 2. 2,13,20

Surgical ManagementThere is no known treatment modality that will reverse

the primary steno-occlusive process, and current treat-ments are designed to improve cerebral blood flow to reduce future stroke risk, reduce moyamoya-associated collaterals, and decrease the frequency of symptoms. Surgical revascularization is the fundamental treatment modality for moyamoya.1,15

Key points of surgical management focus on indications for surgery, timing of the operation, selection of specific technique, and expectations of outcome following revascu-larization. Potential complications of surgery include stroke, infection, and hemorrhage. Tenets of perioperative care to minimize the perioperative stroke risk include careful hydra-tion, often with intravenous fluids at 1 to 1.25 times mainte-nance levels; avoidance of hyperventilation-related cerebral vasoconstriction, which often occurs because of crying, pain, or emesis; effective pain control, strict blood pressure con-trol to maintain cerebral perfusion; and preoperative use of antiplatelet agents (withheld only on the day of surgery then resumed from the first postoperative day).

Indications Indications include radiographic evidence of moyamoya,

including ongoing ischemic symptoms and/or evidence of compromised blood flow or cerebral perfusion reserve. Data also suggest that clinically asymptomatic children who have radiographic or functional evidence of impaired cerebral perfusion should be considered as operative candidates; this position is supported by the American Heart/Stroke Association recommendations. Relative contraindications include very early stage arteriopathy with normal perfusion and/or children with profound medical or neurologic com-promise. Of note, the rare data focused on surgical revascu-larization in individuals with ACTA2 moyamoya suggest that this is a very high-risk population.21,22

TimingTiming of surgery ideally minimizes the duration between

diagnosis and revascularization; however, delays of several

ACTA2 R179

BRCC3/MTCPI

GUCYIA3

RNF213

SAMHD1

Box 2. Genetic Mutations Associated with Moyamoya



weeks may be appropriate to coordinate skilled anesthetic and operating room staffing, or to allow recovery from an acute stroke.15 If possible, the ability to perform bilateral surgery (if indicated) under a single anesthetic may help to reduce complications and speed up the growth of surgical collaterals, particularly in very young patients.23

Surgical Approaches and OutcomesBecause moyamoya arteriopathy affects the ICAs and

spares the ECAs, surgical treatment utilizes ECA branches as a donor source to supply blood flow to the ischemic brain. There are 2 main categories of surgical revasculariza-tion. The first is direct, which involves harvesting a donor vessel (usually superficial temporal artery) and anasto-mosing it directly to a single recipient cortical vessel. The second is indirect (Figure 2), which uses vascularized tissue (eg, an artery, pericranium, or muscle) to stimulate the growth of a new vascular network when placed in contact with the brain.1 Although there is considerable debate about the merits and drawbacks of the 2 approaches, both are effective in reducing the stroke rate in individuals with moyamoya. In some children, however, direct procedures may not be technically feasible because of the delicacy and small caliber of vessels. Recent analyses support the prem-ise that indirect operations may be more durable, with better long-term results in the pediatric population.9

There is abundant evidence that surgical revasculariza-tion improves a wide range of outcome metrics in children with moyamoya. Radiographically, revascularization revers-es white matter changes, improves measures of cerebral oxygenation, and increases cerebral blood flow, stabilizing stroke burden, despite progressive arteriopathy.2 Clinically, surgery decreases ischemic symptoms, headache, and risk

of hemorrhage and markedly reduces stroke rates. Surgery reduces stroke risk at years 1 and 5 from 32% and 66% to 90%, respectively, to less than 5% for most populations at both years 1 and 5. Surgery also improves functional and cognitive outcomes.1,9 These good outcomes are durable, with recent long-term outcomes (>20 years) demonstrat-ing persistence of the surgical collaterals over decades and the continued protection from stroke while participating in all forms of activity (eg, exercise, advanced educational degrees, and childbirth).21

It is increasingly clear that treatment at a high-volume cen-ter with a dedicated pediatric cerebrovascular team is among the most important predictors of surgical outcome. A recent national database analysis revealed that high-volume centers (averaging >30 procedures annually) had shorter lengths of stay (32%), lower costs (57%), 8-fold more likely discharge to home (versus rehabilitation), and a 15-fold lower rate of death.24,25 These data support the regionalization of care with centers of excellence for subspecialized care.

ConclusionsMoyamoya represents a constellation of arteriopathies

that vary in genetic and environmental drivers but share a common end-pathway of progressive internal carotid artery narrowing and collateral development that leads to stroke if untreated. Diagnosis is predicated on character-istic radiographic findings observed on MRI and catheter angiogram, with treatment centered on surgical revascu-larization to reduce the risk of stroke. Surgical treatment is very successful at providing durable substantial reductions in stroke risk particularly when performed at high-volume centers with experienced teams. n

Figure 2. Intraoperative images of an indirect revasculrization procedure (pial synagngiosis) utilizing the superficial temporal artery.

(A) After mapping the parietal branch of the superficial temporal artery with Doppler ultrasonography, a good length of the artery

was microscopically dissected from distal to proximal, leaving a cuff of tissue around it. (B) After performing the craniotomy and

opening the dura widely, the arachnoid was opened in as many areas as possible. Notice the engorged vessels on the “starving brain”

surface reflecting the ischemic process of moyamoya. (C) The donor artery is laid in direct contact with the brain surface and sutured

to the pia using 10-0 nylons. The dural leaflets are laid on the brain without suturing.

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1. Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med. 2009;360(12):1226-1237. 2. Wanebo JE, Khan N, Zabramski J, Spetzler RF. Moyamoya Disease: Diagnosis and Treatment. New York: Thieme; 2014.3. Takeuchi K, Shimizu K. Hypoplasia of the bilateral internal carotid arteries. Brain Nerve. 1957;9:37-434. Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain.

Arch Neurol. 1969;20(3):288-299. doi:10.1001/archneur.1969.004800900760125. Hirotsune N, Meguro T, Kawada S, Nakashima H, Ohmoto T. Long-term follow-up study of patients with unilateral

moyamoya disease. Clin Neurol Neurosurg. 1997;99(Suppl 2):S178-S181. 6. Uchino K, Johnston SC, Becker KJ, Tirschwell DL. Moyamoya disease in Washington State and California. Neurology.

2005;65(6):956-958. 7. Gaillard J, Klein J, Duran D, et al. Incidence, clinical features, and treatment of familial moyamoya in pediatric patients: a

single-institution series. J Neurosurg Pediatr. 2017;19(5):553-559.8. Fung L-WE, Thompson D, Ganesan V. Revascularisation surgery for paediatric moyamoya: a review of the literature.

Childs Nerv Syst. 2005;21(5):358-364. 9. Macyszyn L, Attiah M, Ma TS, et al. Direct versus indirect revascularization procedures for moyamoya disease: a

comparative effectiveness study. J Neurosurg. 2017;126(5):1523-1529. 10. Scott RM, Smith JL, Robertson RL, Madsen JR, Soriano SG, Rockoff MA. Long-term outcome in children with moy-

amoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg Pediatr. 2004;100(2):142-149. 11. Massaro M, Thorarensen O, Liu GT, Maguire AM, Zimmerman RA, Brodsky MC. Morning glory disc anomaly and

moyamoya vessels. Arch Ophthalmol. 1998;116(2):253-254.12. See AP, Ropper AE, Underberg DL, Robertson RL, Scott RM, Smith ER. Down syndrome and moyamoya: clinical presen-

tation and surgical management. J Neurosurg Pediatr. 2015;16(1):58-63. doi:10.3171/2014.12.PEDS1456313. Cecchi AC, Guo D, Ren Z, et al. RNF213 rare variants in an ethnically diverse population with Moyamoya disease. Stroke.

2014;45(11):3200-3207.14. Bower RS, Mallory GW, Nwojo M, Kudva YC, Flemming KD, Meyer FB. Moyamoya disease in a primarily white, midwestern US

population: increased prevalence of autoimmune disease. Stroke. 2013;44(7):1997-1999.15. Smith ER, Scott RM. Spontaneous occlusion of the circle of Willis in children: pediatric moyamoya summary with

proposed evidence-based practice guidelines. A review. J Neurosurg Pediatr. 2012;9(4):353-360. 16. Storey A, Michael Scott R, Robertson R, Smith E. Preoperative transdural collateral vessels in moyamoya as radiographic

biomarkers of disease. J Neurosurg Pediatr. 2017;19(3):289-295.17. Smith ER. Moyamoya Biomarkers. J Korean Neurosurg Soc. 2015;57(6):415-421. doi:10.3340/jkns.2015.57.6.41518. Lin N, Smith ER, Scott RM, Orbach DB. Safety of neuroangiography and embolization in children: complication analysis

of 697 consecutive procedures in 394 patients. J Neurosurg Pediatr. 2015;16(4):432-438. 19. Lin N, Baird L, Koss M, et al. Discovery of asymptomatic moyamoya arteriopathy in pediatric syndromic populations:

radiographic and clinical progression. Neurosurg Focus. 2011;31(6):E6. 20. Guey S, Tournier-Lasserve E, Hervé D, Kossorotoff M. Moyamoya disease and syndromes: from genetics to clinical

management. Appl Clin Genet. 2015;8:49-68. 21. Riordan CP, Storey A, Cote DJ, Smith ER, Scott RM. Results of more than 20 years of follow-up in pediatric patients with

moyamoya disease undergoing pial synangiosis. J Neurosurg Pediatr. March 2019:1-7. 22. Rutledge WC, Choudhri O, Walcott BP, et al. Indirect and direct revascularization of ACTA2 cerebral arteriopathy: fea-

sibility of the superficial temporal artery to anterior cerebral artery bypass with posterior auricular artery interposition graft: case report. J Neurosurg Pediatr. 2016;18(3):339-343.

23. Jackson EM, Lin N, Manjila S, Scott RM, Smith ER. Pial synangiosis in patients with moyamoya younger than 2 years of age. J Neurosurg Pediatr. 2014;13(4):420-425.

24. Bekelis K, Connolly ID, Do HM, Choudhri O. Operative volume and outcomes of cerebrovascular neurosurgery in children. J Neurosurg Pediatr. 2016;18(5):623-628. doi:10.3171/2016.5.PEDS16137

25. Titsworth WL, Scott RM, Smith ER. National Analysis of 2454 Pediatric Moyamoya Admissions and the Effect of Hospital Volume on Outcomes. Stroke. 2016;47(5):1303-1311.

Alaa Montaser, MD, PhDDepartment of NeurosurgeryBoston Children’s HospitalHarvard Medical SchoolBoston, MA

Edward R. Smith, MDR. Michael Scott Chair in Neurosurgery Co-DirectorCerebrovascular Surgery and Interventions Center Director, Pediatric Cerebrovascular SurgeryDepartment of Neurosurgery-Vascular Biology ProgramBoston Children’s Hospital-Harvard Medical SchoolBoston, MA

DisclosuresAM reports no disclosures. ERS has disclosures at www.practicalneurology.com

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Moyamoya Diseasev2.practicalneurology.com/pdfs/PN0120_CF4_Moyamoya.pdf · 2020-01-08 · a collateral vascular network of small vessels arising from the carotid artery, leptomeninges,