What is Moya Moya disease?

What is Moyamoya Disease?

Moyamoya is a progressive cerebrovascular arteriopathy characterized by stenosis or occlusion of the terminal internal carotid arteries and their main branches, with compensatory development of an abnormal network of fragile collateral vessels at the base of the brain that appear as a "puff of smoke" on angiography. 1

Disease Definition and Terminology

Moyamoya Disease (MMD) refers to this vascular pattern occurring as an isolated, idiopathic condition without other identifiable causes, typically affecting both sides of the brain bilaterally. 1

Moyamoya Syndrome (MMS) describes the identical angiographic appearance but occurring secondary to associated conditions including:

• Autoimmune diseases (systemic lupus erythematosus, antiphospholipid syndrome, polyarteritis nodosa, Sjogren syndrome) 1
• Sickle cell disease 1
• Down syndrome 1
• Neurofibromatosis type 1 1
• Head irradiation 1
• Brain tumors 1
• Meningitis 1

The 2021 Research Committee on Moyamoya Disease guidelines now accept unilateral disease as sufficient for diagnosis, given evidence that unilateral cases frequently progress to bilateral involvement. 1

Pathophysiology and Natural History

The arteriopathy involves progressive stenosis centered on the terminal portion of the intracranial internal carotid artery, with the disease evolving through 6 distinct angiographic stages (Suzuki stages) as stenosis worsens and collateral vessels develop then eventually disappear. 1

The disease is relentlessly progressive in nearly all patients, with more than two-thirds experiencing symptomatic progression within 5 years, resulting in permanent neurological deficits. 1 The condition worsens in approximately 20% of both symptomatic and asymptomatic patients, with progression associated with ischemic or hemorrhagic symptoms in over 50% of those who progress. 1

Epidemiology

Moyamoya is most common in East Asian populations, particularly Japan, Korea, and China, with genetic factors playing a significant role—up to 12% of patients have a positive family history. 1, 2 The RNF213 gene mutation is strongly associated with the disease in East Asian populations. 1, 2

In the United States, the incidence is approximately 0.57 per 100,000 people per year, with highest rates among Asian/Pacific Islanders. 1 The disease shows a female predominance with a women-to-men ratio of 2.6:1 in US populations. 1

Clinical Presentations

The disease demonstrates bimodal age distribution with peaks around age 10 and 40 years, though the peak occurs later in women than men. 1, 2

Pediatric Presentation

• Predominantly ischemic symptoms including transient ischemic attacks and stroke 1, 2
• Intellectual decline 2
• Seizures 2
• Involuntary movements 2

Adult Presentation

• Both ischemic and hemorrhagic events 1, 2
• Intracranial hemorrhage more common than in pediatric patients, often accompanied by intraventricular hemorrhage 2
• Transient ischemic attacks 1
• Cognitive deficits 1
• Migraine-like episodes 1
• Psychiatric and movement disorders 1

Patients with posterior circulation involvement may have more severe clinical manifestations at presentation. 1

Diagnostic Criteria

Angiographic Findings (Gold Standard)

Catheter angiography remains the diagnostic method of choice, demonstrating: 1, 2

• Stenosis or occlusion of the terminal internal carotid artery and its main branches 1
• Pathognomonic "puff of smoke" appearance from abnormal collateral vessel networks in the basal ganglia region 1

MRI/MRA Criteria

For diagnosis without catheter angiography (using ≥1.5 Tesla scanners): 1

• Stenosis/occlusion of the terminal internal carotid artery 1
• Decreased outer diameter of the terminal internal carotid artery and horizontal middle cerebral artery bilaterally on heavy T2-weighted MRI 1
• At least 2 visible flow voids (unilateral or bilateral) at the basal ganglia or periventricular white matter representing abnormal vascular networks on MRA 1

T2-weighted FLAIR imaging may show the "ivy sign" (high signal in sulci) indicating slow flow in affected vascular territories. 3

Natural History and Prognosis

Ischemic Presentation

• 5-year stroke risk of 17% and 10-year risk of 33% in conservatively managed patients 1
• For unilateral disease managed conservatively, 5-year risk of recurrent ischemic events is 65% 4
• For bilateral disease managed conservatively, 5-year risk of recurrent ischemic events is 82% 4

Hemorrhagic Presentation

• 5-year stroke risk of 15% and 10-year risk of 40% in conservatively managed patients 1
• Patients with posterior hemorrhage have extremely high rebleeding risk 5

Asymptomatic Patients

• Annual risk of cerebrovascular events approximately 5% 1
• Disease progression occurs in 20% over mean follow-up of 6 years 1

Treatment Principles

Treatment is predicated on restoration of cerebral blood flow by surgical revascularization, as no medical therapy limits progression of the vessel wall lesions. 1 Surgical options include direct bypass (superficial temporal artery to middle cerebral artery anastomosis) and indirect bypass procedures (pial synangiosis). 1, 6

Moyamoya disease accounts for 6% of all childhood strokes despite its rarity, underscoring the importance of recognition and appropriate management. 1