Moyamoya

6 Interesting Facts of Moyamoya

1. Moyamoya disease is a unique chronic progressive cerebrovascular disease characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis with prominent arterial collateral circulation
2. Presentation is marked by ischemic or hemorrhagic stroke in most cases
3. Head CT or brain MRI is used initially to detect cerebral infarcts and hemorrhage; magnetic resonance angiography or conventional catheter angiography is necessary to demonstrate stenoses in the distal internal carotid arteries or collateral vessels in the circle of Willis
4. Main treatment is surgical revascularization; antiplatelet therapy with aspirin may be used, but its effectiveness in preventing strokes is uncertain
5. Use calcium channel blockers to treat headaches and antiepileptics to prevent seizures
6. Surgical revascularization reduces risk of stroke, but even surgically treated patients with moyamoya continue to have increased lifelong risk of stroke thereafter

Pitfalls

• Use of IV tissue plasminogen activator is contraindicated for moyamoya disease manifesting as cerebral ischemia because of the high risk of intracranial bleeding 
• In children, stress, crying, pain, and hyperventilation may worsen cerebral ischemia; use measures to minimize to avoid precipitating stroke
• Prophylactic antiseizure medication is not recommended after intracranial hemorrhage owing to data demonstrating higher mortality rates and disability, and no reduction in incident seizures 

Moyamoya is a cerebrovascular disorder characterized by chronic progressive stenosis of the intracranial internal carotid arteries and their proximal branches

Moyamoya is a Japanese term that means “puff of smoke,” describing the radiographic appearance of the disease 

Over time, occlusion of internal carotid arteries occurs with concomitant development of collateral vessels at the base of the brain

Major clinical consequences of vessel narrowing are reduced cerebral blood flow and increased risk of stroke

Moyamoya disease describes the condition in which bilateral stenoses are idiopathic in nature, in the absence of other conditions 

Moyamoya syndrome is the terminology used when arteriopathy is unilateral and occurs in association with underlying systemic diseases

Classification

• Suzuki stages of angiographic progression of moyamoya 
  • Stage I: stenosis of both intracranial carotid arteries
  • Stage II: initial moyamoya collateral vessels develop at the base of the brain
  • Stage III: moyamoya collateral vessels become prominent as anterior circulation becomes progressively stenotic and occlusive
  • Stage IV: moyamoya collateral vessels involve posterior circulation
  • Stage V: moyamoya vessels reduce in number and caliber
  • Stage VI: moyamoya collateral vessels begin to disappear

Clinical Presentation

Clinical presentation varies, ranging from headache to seizures, stroke, and intracranial hemorrhage

• Children with moyamoya disease usually suffer ischemic events (70%-80%), whereas adults may have either ischemic or hemorrhagic events 
• A small percentage of patients are asymptomatic and disease is discovered incidentally 

History

• Headache 
  • Particularly common in children 
  • Can be global or unilateral, often worse with hyperventilation or dehydration
  • Headache is migraine like and often refractory to medical therapies
• Speech (eg, dysarthria) and/or visual (eg, transient blindness, loss of visual field) disturbances 
• Motor weakness of face, arm, or leg 
• Cognitive impairment and intellectual decline 

Physical examination

• Hemiparesis: may be transient—lasting minutes to hours—or permanent 
• Sensory impairment
• Aphasia
• Involuntary limb movements (ie, chorea), due to damage to the basal ganglia 
• Seizure activity (occurs in about 5%) 
• Visual field defects or conjugate gaze deviation

Causes

• Precise cause is unclear; multiple conditions exhibit the same end-pathway arteriographic changes 
• Vessel occlusion results from a combination of smooth muscle cell hyperplasia and luminal arterial thrombosis that contributes to vessel narrowing
  • Atherosclerotic deposits and dissection do not play a role 
• Both environmental and genetic factors influence the development of moyamoya 

Risk factors and/or associations

Age

• Bimodal age distribution: 1 peak in childhood and 1 peak in middle adulthood (age 30-40 years) 
• Moyamoya affects young children in particular; half of patients are identified by age 10 years 

Sex

• Female predominance; female to male ratio is approximately 1.8:1 or 2.2:1 

Genetics

• Positive family history in 9% to 15% of Asian patients 
• Several inheritance patterns exist: autosomal dominant with incomplete penetrance, autosomal recessive, X-linked recessive, and polygenic inheritance
• An association between moyamoya disease and genetic loci on chromosome 17q25.3 has been demonstrated and replicated in several analyses 
  • The c.14576G>A polymorphism within the RNF213 gene, encoding RING finger protein 213, is a high-risk allelic variant for moyamoya disease among East Asians (but not among white patients or others who are not of Asian ancestry) 
    • RNF213 gene encodes RING finger protein 213, which has putative function involved in angiogenesis
• Unusual forms of moyamoya disease are caused by mutations in ACTA2 or GUCY1A3, or by deletion of BRCC3 

Ethnicity/race

• More common in people of East Asian descent (eg, Korea, Japan) than in those from the Western Hemisphere 
• Highest prevalence is found in Japan, where it is 4 to 13 times more common than in the United States 
  • Prevalence in Japan: 3.16 to 10.5 per 100,000 people 
  • Prevalence in United States: 0.086 per 100,000 people 

Other risk factors/associations

• Well-established associations
  • Radiation therapy of the head or neck to treat optic gliomas, craniopharyngiomas, and pituitary tumors 
  • Down syndrome 
  • Neurofibromatosis type 1 
  • Sickle cell anemia 
• Less well-established associations
  • Chronic meningitis
  • Thrombophilia
  • Vasculitis due to systemic lupus erythematosus, polyarteritis nodosa, or antiphospholipid antibody syndrome
  • Marfan syndrome
  • Sarcoidosis

How is Moyamoya diagnosed?

• Consider moyamoya in any child or young adult with symptoms or clinical evidence of cerebral ischemia or hemorrhage
• Evaluate cerebral arterial circulation in all patients
  • Often begins with non–contrast-enhanced CT of the head; initial studies are identical to those done to evaluate for ischemic or hemorrhagic stroke
    • Although CT of the head is often used in emergency situations to evaluate for suspected stroke or intracranial hemorrhage, diagnostically—for moyamoya—it is of limited use
  • Diagnosis largely relies on demonstrating typical findings on MRI scans, magnetic resonance angiography, and conventional catheter angiography 
    • MRI, which is always used in the work-up, shows evidence of slow flow, reveals the characteristic collateral vessels in the region of the basal ganglia, and demonstrates old and new infarcts
    • Magnetic resonance angiography, as an additional noninvasive imaging study, reveals presence of moyamoya arteriopathy and may be used in conjunction with MRI to make a presumptive diagnosis of moyamoya
    • Catheter angiography has been the gold standard for confirming the diagnosis. Ideally, it is performed on all patients in whom magnetic resonance angiography or MRI are not definitive, and to aid with surgical planning and follow-up in cases amenable to surgery
      • Catheter angiography presently is not necessary for definitive diagnosis if objective findings on MRI scans and magnetic resonance angiography clearly fulfill the criteria
    • Some experts advocate additional cerebral blood flow studies that reflect physiologic status of affected regions (eg, xenon-enhanced CT scan, PET scan) 
• Consider etiologic investigation for underlying systemic disease in patients in whom there is no obvious predisposing cause
  • Evaluate for potential underlying medical conditions after discovering a moyamoya arteriopathy 
    • Carotid ultrasonographic scan to detect atherosclerosis
    • Cerebrospinal fluid analysis to detect chronic meningitis
    • Antinuclear antibody test and erythrocyte sedimentation rate to detect autoimmune vasculitis
    • Coagulation tests to detect prothrombotic disorders
• Consider genetic testing, which may provide ancillary support for diagnosis in certain patients (eg, Asian ethnicity or presence of systemic [ie, nonatherosclerotic] vasculopathy) 

Laboratory

• Antinuclear antibody test and erythrocyte sedimentation rate
  • Detection of antinuclear antibody, particularly at a dilution of 1:160 or beyond, serves as a screen for vasculitis or systemic lupus erythematosus or other autoimmune disorder, and prompts consultation with a rheumatologist for further evaluation 
  • Modestly elevated erythrocyte sedimentation rate not only can occur in vasculitis but also may be observed in inflammatory conditions such as infection, malignancy, and renal disease 
• Coagulation tests 
  • If there are results outside the reference range, consult hematologist to determine cause of hypercoagulable state
    • Antithrombin III
    • Protein C and protein S
    • Factor V Leiden gene mutation
    • Prothrombin gene mutation
    • Antiphospholipid antibody
• Genetic testing 
  • Sequence analysis of the coding region of RNF213 in patients of Asian ancestry or ACTA2 in patients with systemic vascular disease may reveal predisposition
    • Presence of the c.14576G>A polymorphism in the RNF213 region in Asian patients
    • ACTA2 mutations
      • Testing may be triggered by a unique magnetic resonance angiography pattern demonstrating markedly dilated proximal internal carotid arteries and straight, rodlike middle cerebral artery branches
  • Information on laboratories offering this type of testing is available online at the Genetic Testing Registry 

Imaging

• Brain MRI 
  • Always indicated in work-up for moyamoya
  • Findings indicative of moyamoya
    • Reduced flow voids in the internal carotid artery, middle cerebral artery, and anterior cerebral artery plus prominent flow voids from the basal ganglia and thalamic collateral vessels
    • Reduced cortical blood flow marked by a linear bright signal in the sulci on fluid-attenuated inversion recovery sequences, which is referred to as the ivy sign (highly characteristic)
    • Collateral vessels in the region of the basal ganglia, often best seen on T2-weighted images
  • On MRI, acute infarction is best seen with diffusion-weighted imaging, whereas chronic infarction is better demonstrated on T1- and T2-weighted images
    • MRI, when performed with diffusion-weighted imaging, is as sensitive as CT for detecting acute hemorrhage 
  • MRI has limited ability to identify specific collateral networks and areas of marked stenosis, which is why angiography is needed for surgical planning
• Brain magnetic resonance angiography 
  • Performed concurrently and used in conjunction with MRI to demonstrate stenotic lesions in the distal internal carotid arteries and collateral vessels in the circle of Willis
  • Owing to its noninvasive nature, magnetic resonance angiography has superseded traditional catheter angiography as the diagnostic imaging modality of choice for moyamoya, but it must be done with MRI 
  • For magnetic resonance angiography to be used diagnostically in lieu of angiography, magnetic resonance angiography must show bilateral findings plus both of the following: 
    • Stenosis or occlusion of terminal portion of intracranial internal carotid artery or of proximal portion of anterior and/or middle cerebral artery
    • Abnormal vascular networks in the basal ganglia, showing 2 or more visible flow voids
  • Magnetic resonance angiography is also helpful for identifying other causes of stroke (eg, arterial dissection, venous thrombosis, vasculitis, fibromuscular dysplasia) 
• Catheter angiography 
  • Considered gold standard study for diagnosis and essential study for successful surgical planning
    • Angiography is the most accurate procedure to use to obtain detailed mapping of collateral networks 
  • Moyamoya is definitively diagnosed by angiography that shows the following: 
    • Bilateral stenoses of the distal intracranial internal carotid arteries extending to the proximal anterior, middle, and posterior cerebral arteries
    • Abnormal vascular networks near occlusive lesions in the arterial phase
  • Required when diagnosis is uncertain, during presurgical planning, and during postoperative evaluation
    • Critical during presurgical planning for seeing presence of spontaneous transdural collaterals; interruption of them may cause iatrogenic stroke 
  • Can be omitted if findings on MRI scans plus magnetic resonance angiography fulfill criteria and surgery is not considered
• Non–contrast-enhanced head CT
  • Perform immediately (within 20 minutes) if ischemic stroke or intracranial hemorrhage is suspected
  • In moyamoya disease, presence of hemorrhage (hyperdensity) or ischemia (areas of hypodensity) suggestive of stroke is commonly seen on CT scans in the cortical watershed zones, basal ganglia, deep white matter, or periventricular regions 
  • Use of CT scanning alone is not adequate to diagnose moyamoya
• Carotid ultrasonography
  • Used to exclude atherosclerosis of carotid arteries and carotid bifurcation

Functional testing

• Use cerebral hemodynamic and metabolic studies to measure regional cerebral blood flow and cerebrovascular reserve 
  • After securing diagnosis, use xenon-enhanced CT, single-photon emission CT, and PET scans to evaluate cerebral hemodynamic performance
  • Pattern often seen in moyamoya is a compensatory increase of cerebral blood volume by vasodilation and an increase of oxygen fraction extraction
  • Single-photon emission CT may show reduced cerebral blood flow and impaired cerebrovascular reactivity to acetazolamide challenge in the internal carotid artery territory; this finding suggests reduced cerebrovascular reserve
  • Compromised hemodynamic reserve, as determined by these modalities, predicts disease progression; in presence of this finding, consider earlier surgical intervention

Other diagnostic tools

• Formal diagnosis of moyamoya was traditionally defined by 3 angiographic criteria, based on Japanese Ministry of Health and Welfare guidelines 
  • Stenosis of the distal (intracranial) internal carotid artery, up to and including the bifurcation, along with segments of the proximal anterior and middle carotid arteries
  • Dilated basal collateral vessels
  • Bilateral findings (required)
    • Patients with unilateral changes are classified as probable cases, although some of these cases develop bilateral findings during follow-up 

Differential Diagnosis

Most common

• Cervical artery dissection
• Central nervous system vasculitis
• Intracranial atherosclerosis 
• Cerebral small vessel disease 
• Subarachnoid hemorrhage 
• Arteriovenous malformations

Treatment Goals

• Goal of surgical revascularization is to prevent cerebral infarction by improving cerebral blood flow and restoring reserve capacity

Admission criteria

Immediate evaluation of possible stroke

• Urgent management of airway, ventilation, and circulation is vital in patients who have decreased levels of consciousness
• Perform emergency head CT (within 20 minutes) to ascertain whether ischemia or hemorrhage is present 
• Perform MRI with diffusion-weighted images for the identification of completed stroke

Criteria for ICU admission

• Ischemic or hemorrhagic stroke

Recommendations for specialist referral

• Refer to neurologist to evaluate stroke or ischemic symptoms and to prevent progression, or for diagnostic assistance in presence of symptoms possibly related to moyamoya
• Refer to neurosurgeon to evaluate surgical options and optimal timing for patients with symptomatic disease or asymptomatic progressive disease
• For patients with acute cerebral hemorrhage, refer to neurosurgeon for emergency operative decompression or cerebrospinal fluid diversion 

Treatment Options

Current treatments of moyamoya disease are intended to prevent strokes by improving blood flow to the affected cerebral hemisphere, but they do not arrest or reverse the primary disease process 

Neurosurgical revascularization is the cornerstone of treatment

Medical therapy

• For patients with ischemic disease:
  • Antiplatelet therapy is intended to reduce vascular stenosis, but there is limited evidence that it is effective for preventing ischemic stroke 
    • Patients usually continue antiplatelet therapy throughout their lives, including after revascularization 
    • Use of IV tissue plasminogen activator is contraindicated for moyamoya disease manifesting as ischemic stroke because there is high risk for intracranial bleeding 
  • Immediate actions for acute symptoms related to disrupted cerebral blood flow to prevent stroke or its progression:
    • IV hydration with isotonic fluids (usually at 1.25-1.5 times typical maintenance rate) 
    • Avoid hypotension and hyperventilation 
    • Administer supplemental oxygen 
    • In absence of hemorrhage (as demonstrated by CT imaging), consider aspirin to treat acute arterial ischemic stroke
    • Do not administer thrombolytic therapy 
    • For patients with hemorrhagic stroke:
• • In patients whose systolic blood pressure exceeds 150 mm Hg, aim to reduce it to below 140 mm Hg 
    • Although not specific to moyamoya patients, evidence shows that in adult patients with hemorrhagic stroke, reduction to this level is safe and is associated with better outcomes 
    • Avoid hypotension
  • American Heart Association/American Stroke Association guidelines recommend against prophylactic use of antiepileptic drugs in patients who have hemorrhagic strokes, but they favor antiepileptic drugs in patients who experience seizures. Levitricam or phenobarbital are recommended by some experts
• Prescribe calcium channel blockers to ease intractable headache or migraine, commonly seen in patients with moyamoya 
• In general, there is poor response to medical therapy and disease is progressive without operative intervention
• Lifestyle modifications
  • Patients with moyamoya should aim to incorporate specific lifestyle practices to reduce the likelihood of triggering vasospasm or ischemic event (eg, avoid smoking and using stimulants, avoid hyperventilating)

Drug therapy

• Antiplatelet therapy
  • Evidence supporting effectiveness in preventing stroke is insufficient, but aspirin is routinely prescribed in ischemic disease 
  • Aspirin
    • Aspirin Chewable tablet; Infants, Children, and Adolescents: the usual dose is 50 to 100 mg PO daily 
    • Aspirin Oral tablet; Adults: Optimal dosage is not defined, 325 mg PO daily is reasonable 
• Calcium channel blocker (treatment of headaches)
  • Treatment of intractable headache or migraine
  • Verapamil
    • Use cautiously owing to theoretical concern that lowering blood pressure has the potential to reduce cerebral perfusion
    • There is limited published dosing information for pediatric patients; experienced neurologist should guide use
    • Verapamil Hydrochloride Oral tablet; Adults: Dosage not established. 80 mg PO 3 to 4 times daily has been studied.
• Antiepileptic
  • Levetiracetam
    • Levetiracetam Oral solution; Infants 1 to 5 months: Initially, 7 mg/kg/dose PO twice daily. Increase dose every 2 weeks by 7 mg/kg/dose (i.e., 14 mg/kg/day) to goal of 21 mg/kg/dose twice daily; dose may be reduced if not tolerated.
    • Levetiracetam Oral solution; Infants and Children 6 months to 3 years: Initially, 10 mg/kg/dose PO twice daily. Increase dose every 2 weeks by 10 mg/kg/dose (i.e., 20 mg/kg/day) to goal of 25 mg/kg/dose twice daily; dose may be reduced if not tolerated.
    • Levetiracetam Oral solution; Children and Adolescents 4 to 15 years: Initially, 10 mg/kg/dose PO twice daily. Increase dose every 2 weeks by 10 mg/kg/dose (i.e., 20 mg/kg/day) to goal of 30 mg/kg/dose twice daily; dose may be reduced if not tolerated.
    • Levetiracetam Oral tablet; Adolescents 16 to 17 years: Initially, 500 mg PO twice daily. Increase dose every 2 weeks by 500 mg/dose (i.e., 1,000 mg/day) to 1,500 mg PO twice daily. Max: 3,000 mg/day.
    • Levetiracetam Oral tablet; Adults: Initially, 500 mg PO twice daily. Increase dose every 2 weeks by 500 mg/dose (i.e., 1,000 mg/day) to 1,500 mg PO twice daily. Max: 3,000 mg/day.
  • Phenobarbital
    • Phenobarbital Oral solution; Infants and Children 6 years and younger: 4 to 8 mg/kg/day PO or IV/IM in 1 to 2 divided doses; titrate based on patient response and serum concentration. Higher doses (up to 10 mg/kg/day) may be necessary in younger children.
    • Phenobarbital Oral solution; Children and Adolescents 7 years and older: 3 to 6 mg/kg/day PO or IV/IM in 1 to 2 divided doses; titrate based on patient response and serum concentration.
    • Phenobarbital Oral tablet; Adults: 1 to 3 mg/kg/day PO or IV/IM in 1 to 2 divided doses; titrate based on patient response and serum concentration.

Nondrug and supportive care

Lifestyle modifications

• All patients should avoid dehydration and hyperventilation 
• All patients should avoid smoking tobacco and using recreational drugs, especially those that cause vasospasm (eg, cocaine)
• After revascularization most patients can tolerate normal activity, including sports, but they need to avoid activities in which head injury is common (eg, boxing, football) or in which extremes of barometric pressure occur (eg, skydiving, scuba diving)
• In children stress, crying, pain, and hyperventilation may worsen cerebral ischemia; use minimization measures to avoid precipitating stroke

Perioperative management strategies to reduce surgical complications 

• Stabilize hemodynamics (avoid hypotension) and optimize metabolic state before surgery
• Provide oral or IV (1.25-1.5 times maintenance rate) fluids liberally to ensure euvolemia
• Maintain normocapnia at all times intraoperatively; hypercapnia can aggravate hypoperfusion during surgery
• Provide appropriate analgesia and sedation to minimize pain to reduce likelihood of hyperventilation

Procedures

Revascularization surgery

General explanation

• Surgical revascularization procedures are used to augment cerebral blood flow and increase vascular reserve capacity
• Neurosurgical techniques fall into 3 main categories: 
  • Direct revascularization with microvascular extracranial-to-intracranial bypass
    • Divide a branch of the external carotid artery (usually superficial temporal artery) and anastomose it to a cortical artery, which is typically a distal branch of the middle cerebral artery
  • Indirect revascularization without microvascular anastomotic procedures
    • Place mobilized vascularized tissues (ie, dura, muscle, pedicles) in contact with the brain to facilitate ingrowth of new vessels to the cortex
  • Combined indirect and direct approaches 
    • Uses both direct (to quickly restore cerebral blood flow) and indirect (to increase blood flow over time) revascularization techniques
• Factors to consider when selecting surgical technique: 
  • Direct revascularization
    • Can immediately restore blood flow to ischemic areas; however, in so doing, can lead to hyperperfusion syndrome as a complication
    • Direct bypass 
      • Performed in patients with occlusive disease of the internal or middle cerebral artery
      • Most successful when vascular diameter is sufficient for the superficial temporal artery and cortical (ie, recipient) arteries 
      • Direct procedure is technically difficult, requiring a highly trained surgeon 
  • Indirect revascularization
    • Aimed at stimulating development of new vascular networks; thought to lead to delayed collateralization, but extent of revascularization is considered unpredictable
    • Indirect procedures take more time to improve cerebral blood flow than direct procedures because neovascularization from connective tissue is not immediate 
    • Indirect procedures may be ideal in young pediatric patients or adult patients with advanced moyamoya disease owing to the small caliber of the recipient artery 
• In adults, a combination of direct (superior temporal artery–middle cerebral artery bypass) and indirect revascularization is considered the procedure of choice in most cases 

Indication

• Operative indications are broad; most patients with documented moyamoya should be considered for surgery
• Children: revascularization surgery is indicated in most children because the disease is highly progressive 
• Adults: indications for revascularization in adults include radiographic evidence of moyamoya and either of the following: 
  • Symptomatic moyamoya at any Suzuki stage
  • Asymptomatic moyamoya with Suzuki stages II through VI and/or evidence of progressive radiographic changes suggestive of ischemia (eg, changes on fluid-attenuated inversion recovery MRI or worsening perfusion on arterial spin labeling)

Contraindications

• Stroke within 4 to 6 weeks of planned surgery because there is increased risk of complications in a recently infarcted and edematous brain 
• Coexisting medical conditions that render surgical risk unacceptable

Complications

• Direct revascularization 
  • Hyperperfusion syndrome, which causes neurologic dysfunction and can potentially lead to intracranial hemorrhage
  • Bypass vessel occlusion or atrophy
  • Scalp ischemia, necrosis, and infection
• Indirect revascularization
  • Temporary intraoperative reduction in cerebral blood flow leading to ischemia

Interpretation of results

• Adults with moyamoya: in most series, bypass surgery reduces risk of future stroke events compared with conservative treatments 
• Children with either symptomatic or asymptomatic disease: surgery is increasingly recommended; there is evidence of significant reduction in stroke risk 
• Patients with moyamoya: available evidence, which is low quality, is contradictory with respect to which procedure (ie, indirect, direct, combined) is most effective for preventing recurrent stroke
  • No randomized controlled trials clearly demonstrate 1 technique (ie, indirect, direct, combined) to be superior Adults: 1 meta-analysis determined that direct revascularization procedures were superior to indirect procedures for preventing future strokes 
  • Separate comprehensive literature search found that indirect and combination revascularization procedures were superior to direct methods in children at 5 to 10 years postoperatively and in adults at 4 years postoperatively 
  • Retrospective review of medical records found that effectiveness of various revascularization methods (ie, direct, indirect, and combined procedures) were statistically similar in terms of preventing future ischemic strokes in adults with moyamoya 
  • Review of outcomes in 1156 children treated surgically concluded that 87% showed symptomatic benefit from surgical revascularization, with indirect and direct/combined techniques demonstrating equal effectiveness at reducing ischemic symptoms 
  • Randomized controlled trial in Japan found that extracranial-intracranial bypass procedure for hemorrhagic moyamoya disease is marginally effective in preventing rebleeding (risk of a rebleeding event 2.7% per year for surgery versus 7.6% per year for nonsurgery) 

Special populations

• Patients with sickle cell disease
  • 10% of those with both sickle cell anemia and moyamoya have ischemic stroke before age 20 years 
  • Medical therapy is less likely to be effective in this group, and most experts favor cerebral vascularization soon after the diagnosis is made 

Monitoring

• Routine surveillance of all patients with moyamoya is recommended because they have an increased lifelong risk of stroke
  • Some experts recommend a follow-up MRI 3 to 6 months after surgery to ensure patency of grafts and to establish a baseline for subsequent comparison
  • Once postsurgical recovery is complete, patient has follow-up visits to neurosurgeon annually for 3 to 5 years, then periodically thereafter 
• Follow-up of patients with initially discovered unilateral arteriopathy is particularly important because of the high risk of development and/or progression of disease on the unaffected side 
  • Obtain annual imaging with MRI or magnetic resonance angiography for at least 3 to 5 years, with office visits annually thereafter 

Complications

• Complications of disease
  • Ischemic stroke
  • Hemorrhagic stroke
  • Seizures
• Complications of surgery
  • Direct revascularization
    • Hyperperfusion syndrome
    • Bypass vessel occlusion or atrophy
    • Scalp ischemia, necrosis, and infection
  • Indirect revascularization
    • Temporary intraoperative reduction in cerebral blood flow leading to ischemia

Prognosis

• All patients with moyamoya have a lifelong risk of stroke, even after surgical treatment 
• Natural history of untreated or medically treated disease
  • Both arteriopathy and clinical symptoms inevitably progress in untreated patients 
  • Rate of disease progression is high in asymptomatic patients who do not undergo revascularization surgery 
    • Majority of asymptomatic patients (particularly younger children) with moyamoya develop radiographic progression and/or overt symptoms within 5 years or less 
    • Annual risk for stroke of any type is approximately 3% 
  • Disease progression in symptomatic children or adults
    • Deterioration is especially common among children 
    • Annual risk for stroke in adults is estimated at 10% to 15% per year 
• Surgically treated disease
  • Symptoms improve in the majority (greater than 85%) of patients who undergo surgery 
    • Review of 1156 children with moyamoya treated surgically found that 87% derived symptomatic benefit from surgical revascularization, with indirect and direct/combined techniques demonstrating equal effectiveness 
  • Risk of perioperative stroke, subsequent ipsilateral stroke, or death after surgery is about 17% over a 5-year span 

Screening

At-risk populations

• At-risk populations include those who have sickle cell disease and those with first-degree relatives who have known moyamoya; however, screening of asymptomatic patients in these groups is not currently recommended 

Screening tests

• Screening asymptomatic populations, even if high risk, is not currently recommended; however, emerging studies show the combination of magnetic resonance angiography and genotyping of RNF213 p.R4810K variant may be useful for identifying an elevated risk for steno-occlusive intracranial arterial diseases in family members of a person with moyamoya

Sources

Scott RM et al: Moyamoya disease and moyamoya syndrome. N Engl J Med. 360(12):1226-37, 2009 Reference