A patient, typically a child or young adult, presenting with transient ischemic attacks (TIAs), strokes, or headache, characterised by a hallmark pathological feature of progressive stenosis of the terminal portion of the internal carotid arteries and their branches, leading to the development of a network of abnormal collateral vessels that appear as a puff of smoke (moyamoya in Japanese) on cerebral angiography.
Description
Moyamoya disease is a rare, progressive cerebrovascular disorder characterised by chronic stenosis or occlusion at the terminal portion of the internal carotid arteries and the development of a compensatory network of tiny, fragile collateral vessels. These vessels provide a bypass for cerebral blood flow but are prone to haemorrhage and can lead to ischaemic or haemorrhagic strokes. The disease has a bimodal age distribution, primarily affecting children and young adults, and shows a predilection for females and individuals of Asian descent.
Pathogenesis
The exact cause of Moyamoya disease is unknown, but it is believed to involve genetic and environmental factors. Genetic susceptibility has been suggested, with mutations in the RNF213 gene identified in some populations. The disease process involves intimal thickening and proliferation of smooth muscle cells, leading to luminal narrowing and eventual occlusion of affected vessels. The characteristic puff of smoke appearance on imaging results from the proliferation of collateral vessels attempting to bypass the stenotic segments.
Epidemiology, Risk Factors & Associations
- Predominantly affects individuals of Asian descent, particularly Japanese and Koreans.
- Female predominance.
- Two age peaks: early childhood and the fourth decade of life.
- Familial cases (15%) suggest a genetic component.
- Associated conditions include sickle cell disease, Down syndrome, neurofibromatosis type 1 and radiation exposure.
Clinical Features
- TIAs and ischaemic strokes, presenting with hemiparesis, aphasia, or seizures.
- Headaches, often severe and resembling migraines.
- In adults, intracranial haemorrhage is more common than in children.
- Cognitive decline and psychiatric symptoms may develop over time.
Complications
- Recurrent strokes leading to cumulative neurological deficits.
- Intracranial haemorrhage from fragile collateral vessels.
- Cognitive impairment and reduced quality of life.
Pathological Features
Histopathology
- Macroscopic: Narrowing or occlusion of the terminal internal carotid arteries and their branches, with an extensive network of small collateral vessels.
- Microscopic: Fibrocellular thickening of the intima, with reduced elastic fibers in the media and proliferation of the vascular endothelium.
Radiological Features
General Features
- The first-line investigation for Moyamoya disease is MRI/MRA, with DSA serving as the gold standard for definitive diagnosis.
- Characteristically demonstrates stenosis or occlusion of the terminal internal carotid arteries and a network of tiny collateral vessels producing a puff of smoke appearance. This is most pronounced in the basal ganglia and thalamic regions.
- The puff of smoke sign, noted on cerebral angiography, is indicative of the collateral vascular networks that develop in response to arterial stenosis.
- Image appearances of associated features may include ischaemic changes in the brain, particularly in watershed areas, due to chronic hypoperfusion. These can be succinctly identified on MRI.
- Paediatric presentations are typically more ischaemic as they often may be yet to develop collateral vessels.
- Additional findings may include evidence of previous strokes or microbleeds, especially in adults, and complications such as intracranial haemorrhage.
- Complications visualised on imaging may include ischaemic stroke from reduced cerebral perfusion and haemorrhagic stroke from rupture of the fragile collateral vessels.
CT
- Non-contrast: May show evidence of ischaemic stroke or intracranial haemorrhage but is less sensitive for detecting Moyamoya vessels.
- C+ Arterial and Venous phases: Contrast-enhanced CT angiography can demonstrate stenosis of the cerebral arteries and collateral vessels but with less detail than MRA or DSA.
MRI
- High-resolution MRI and MRA are preferred for visualising the stenosis of cerebral arteries and the network of Moyamoya vessels.
- T1: Ischaemic areas may appear hypointense; areas of haemorrhage may show high signal in subacute stages.
- T2: Shows high signal in ischaemic areas; ivy sign indicating leptomeningeal enhancement and collateral circulation.
- FLAIR: Useful for identifying ischaemic lesions and the ivy sign representing prominent leptomeningeal collaterals due to slow flow.
- DWI/ADC: Acute ischaemic strokes show restricted diffusion on DWI with corresponding low signal on ADC maps.
- T1 Gad+: May show enhancement of the Moyamoya vessels and leptomeningeal collaterals.
- MRA: Narrowing of the internal carotid artery terminus and proximal M1 segments bilaterally. Narrowing of the A1 segments with reconstitution of dimunitive distal anterior cerebral arteries may be seen.
- SWI/GRE/T2*: Sensitive for detecting microbleeds and haemosiderin deposition, which are more common in adult patients.
- In-Out-Phase imaging: Not typically used for Moyamoya disease but can be useful for identifying microhaemorrhages or calcifications if present.
NM
- PET FDG: Not routinely used in Moyamoya disease but can assess cerebral perfusion and metabolism, potentially identifying areas of reduced perfusion or metabolic activity.
Grading and Staging
Suzuki Staging System
Moyamoya disease is graded based on angiographic findings, with stages indicating the progression of arterial stenosis and collateral vessel formation. The Suzuki staging system is the most widely used:
- Stage 1: Narrowing of the carotid fork
Initial stenosis of the terminal portion of the internal carotid artery (ICA). - Stage 2: Initiation of Moyamoya vessels
Progressive stenosis of the ICA with the beginning of abnormal collateral vessel formation (Moyamoya vessels) around the circle of Willis. - Stage 3: Intensification of Moyamoya vessels
Advanced stenosis with a well-developed network of Moyamoya vessels, significant reduction in blood flow through the ICA. - Stage 4: Minimisation of Moyamoya vessels
Collateral Moyamoya vessels begin to diminish as the steno-occlusive process continues, and the posterior circulation starts compensating. - Stage 5: Reduction of Moyamoya vessels
Further reduction of Moyamoya vessels, increased involvement of collateral circulation from the external carotid artery (ECA) and posterior circulation. - Stage 6: Disappearance of Moyamoya vessels
Complete occlusion of the ICA with disappearance of Moyamoya vessels, reliance on collateral circulation from ECA and posterior circulation.
Differential Diagnosis
- Atherosclerotic cerebrovascular disease: Typically affects older adults and involves different vascular distributions.
- Vasculitis: Involves inflammation of the vessels and can be differentiated by clinical presentation and laboratory markers of inflammation.
- Arterial dissection: Usually presents acutely with localized symptoms and can be identified by imaging.
Management
- Medical management includes antiplatelet therapy for ischaemic symptoms and anticonvulsants for seizures.
- Surgical revascularisation, such as direct (superficial temporal artery to middle cerebral artery STA-MCA bypass) or indirect (encephaloduroarteriosynangiosis) techniques, is often considered to improve cerebral blood flow and reduce the risk of stroke.
- Management of risk factors and associated conditions.