Moyamoya Disease is a progressive neurodegenerative disorder characterized by the gradual loss of neuronal function. This page provides comprehensive information about the disease, including its pathophysiology, clinical presentation, diagnosis, and current therapeutic approaches.
**Disease Name**: Moya Disease
**Classification**: Cerebrovascular Disorder / Chronic Progressive Vasculopathy
**Type**: Idiopathic (Moya Disease) vs. Associated with other conditions (Moya Syndrome)
**Onset**: Childhood (peak 5-10 years) or adulthood (30-40 years)
**Prevalence**: 0.5-1 per 100,000 in East Asia; 0.1 per 100,000 in Western populations
**ICD-10 Code**: I67.5
**OMIM**: 607151
Moya Disease is a rare, chronic, progressive cerebrovascular disorder characterized by the bilateral stenosis or occlusion of the arteries at the base of the brain (the terminal internal carotid arteries and the proximal anterior and middle cerebral arteries). The name "Moya" means "puff of smoke" in Japanese, describing the appearance of the compensating collateral vessels that form at the base of the brain[1].
This disease leads to reduced blood flow to the brain (cerebral hypoperfusion)[1], which can cause transient ischemic attacks (TIAs), strokes, seizures, and progressive cognitive decline. Moya primarily affects children, but adults can also be affected, with females slightly more commonly affected than males.
- Highest prevalence in East Asian populations, particularly Japan, Korea, and China
- Significantly lower incidence in Western populations
- Accounts for approximately 6% of all pediatric cerebrovascular diseases in Japan[2]
- Pediatric form: Peak onset at 5-10 years
- Adult form: Peak onset at 30-40 years
- Approximately 5-10% of cases are familial
- Genetic predisposition (RNF213 gene mutations)[3]
- Female sex (slight female predominance)
- Family history (5-10% of cases)
- Associated conditions in Moya syndrome
The disease is characterized by[2]:
- Progressive stenosis/occlusion: Of the terminal internal carotid arteries (ICA) and proximal anterior cerebral arteries (ACA) and middle cerebral arteries (MCA)[4]
- Intimal thickening: Thickening of the inner layer of blood vessels
- Dilated collateral vessels: Formation of abnormal collateral networks (Moya vessels)
- Loss of smooth muscle cells: In the arterial media
The characteristic "puff of smoke" appearance comes from[4]:
- Dilated basal ganglia perforating arteries
- Leptomeningeal anastomoses
- Transdural anastomoses
- Ethmoidal collateral vessels
These collaterals are fragile and prone to hemorrhage[5].
- Reduced cerebral blood flow (CBF), particularly in the anterior circulation
- Impaired cerebrovascular autoregulation
- Increased oxygen extraction fraction
- Luxury perfusion in some regions
Primary vasculopathy with no identifiable underlying cause[1].
Moya-like vascular changes associated with other conditions:
- Down syndrome
- Neurofibromatosis type 1
- Sickle cell disease
- Cranial radiation therapy
- Autoimmune diseases
- Congenital heart disease
| Stage |
Findings |
| 1 |
Terminal ICA stenosis |
| 2 |
Initiation of Moya vessels |
| 3 |
Prominent Moya vessels |
| 4 |
Reduction of Moya vessels |
| 5 |
Disappearance of Moya vessels |
| 6 |
Formation of external carotid collaterals |
- Transient ischemic attacks (TIAs): Often triggered by hyperventilation, crying, or exercise
- Ischemic stroke: Particularly in the watershed territories
- Seizures: Focal or generalized
- Headache: Recurrent, often migrainous
- Cognitive decline: Progressive decline in school performance
- Movement disorders: Especially in younger children
- Hemorrhagic stroke: More common than in children (30-40% of adult cases)[5]
- TIA or ischemic stroke: Less common than hemorrhage
- Seizures
- Cognitive impairment
- Headache
- Anterior circulation: Hemiparesis, aphasia, cognitive deficits
- Posterior circulation: Visual symptoms, vertigo, ataxia
- Watershed territories: Bilateral symptoms, transcortical motor aphasia
- Shows vessel dropout in the basal ganglia region
- Evidence of old or acute infarcts
- Hemorrhage in adult cases
- "Ivy sign" on FLAIR sequences (leptomeningeal enhancement)
- Non-invasive visualization of the steno-occlusive changes
- Shows collateral Moya vessels
- Can be used for screening and follow-up
- Gold standard for diagnosis
- Demonstrates the characteristic "puff of smoke" appearance
- Shows all six stages of Suzuki classification
- Evaluates collateral circulation[6]
- Useful for rapid evaluation
- Shows vessel changes and collateral circulation
- Genetic testing: RNF213 gene mutations (particularly in Asian populations)
- Routine bloodwork: To rule out other causes
- Inflammatory markers: To exclude vasculitis
- Cerebrospinal fluid (CSF): Typically normal
- EEG: May show slow waves in affected regions
- Antiplatelet agents: Aspirin, clopidogrel (may reduce TIA frequency)
- Anticoagulants: In selected cases (e.g., with cardioembolic risk)
- Seizure control: Antiepileptic drugs as needed
- Blood pressure management: Maintain adequate cerebral perfusion
- Avoid triggers: Hyperventilation, dehydration, extreme temperatures
- Superficial temporal artery (STA) to middle cerebral artery (MCA) bypass[7]
- Immediate improvement in blood flow
- Technically challenging, especially in children
- High patency rates in experienced centers
- Encephaloduroarteriosynangiosis (EDAS)
- Encephalomyosynangiosis (EMS)
- Multiple burr holes
- Safer in children
- Gradual revascularization over months
- Both direct and indirect bypass
- Often performed in adult patients
- Blood pressure monitoring and management
- Antiplatelet therapy
- Serial imaging to assess bypass patency
- Rehabilitation for stroke-related deficits
- Progressive disease in most cases
- Approximately 5-10% of patients remain stable
- Higher risk of stroke in patients with frequent TIAs
- Better prognosis: Younger age at onset, STA-MCA bypass surgery[8]
- Worse prognosis: Frequent TIAs, advanced Suzuki stage, hemorrhage at presentation
- Cognitive outcomes depend on timing of intervention
- Recurrent strokes can lead to permanent neurological deficits
- Quality of life generally good after successful revascularization
Moya syndrome can be associated with:
- Down syndrome
- Neurofibromatosis type 1
- Sickle cell disease
- Thalassemia
- Craniofacial syndromes
- Autoimmune vasculitis
- Antiphospholipid syndrome
- Thyroid disease
- RNF213 gene identification
- Understanding genotype-phenotype relationships
- Family screening protocols
- Serum and CSF markers of disease activity
- Predictors of disease progression
- Novel revascularization techniques
- Medical therapies to slow progression
- Stem cell therapies
The study of Moyamoya Disease has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Suzuki J, Takaku A. Cerebrovascular "moya" disease. Disease showing abnormal net-like vessels in base of brain. Archives of Neurology. 1969;20(3):288-299. DOI:10.1001/archneur.1969.00480100074003
- Kim JS. Moya disease: epidemiology, clinical features, and diagnosis. Journal of Stroke. 2015;17(1):2-11. DOI:10.5853/jos.2015.17.1.2
- Liu W, Morito D, Takashima S, et al. Identification of RNF213 as a susceptibility gene for Moya disease. Journal of Human Genetics. 2011;56(4):290-295. DOI:10.1038/jhg.2011.8
- Scott RM, Smith ER. Moya disease and Moya syndrome. New England Journal of Medicine. 2009;360(12):1226-1237. DOI:10.1056/NEJMra0804622
- Hallemeier CL, Rich KM, Grubb RL Jr, et al. Clinical features and outcome in North American adults with Moya phenomenon. Stroke. 2006;37(6):1490-1496. DOI:10.1161/01.STR.0000221788.67572.ba
- Fujimura M, Tominaga T. Current status of revascularization surgery for Moya disease. Neurologia Medico-Chirurgica. 2015;55(3):208-215. DOI:10.2176/nmc.ra.2014-0327
- Guzman R, Steinberg M, Dhall S, et al. Direct and indirect revascularization for pediatric Moya disease. Neurosurgery. 2010;67(5):1368-1380. DOI:10.1227/NEU.0b013e3181f33896
- Kuroda S, Houkin K. Moya disease: current concepts and future perspectives. Lancet Neurology. 2008;7(11):1056-1066. DOI:10.1016/S1474-4422(0870240-0