J Stroke.  2025 Jan;27(1):1-18. 10.5853/jos.2024.04273.

Medical Management of Adult Moyamoya Disease: A Review and Relevant Cases With Ischemic Events

• Bang OY
• Fujimura M

• KMID: 2564258
• DOI: http://doi.org/10.5853/jos.2024.04273

Abstract

Moyamoya disease (MMD) is a rare and progressive cerebrovascular disorder characterized by stenosis or occlusion of the internal carotid arteries resulting in the development of fragile collateral vessels at the base of the brain. Surgical revascularization is the primary treatment option for preventing ischemic and hemorrhagic events; however, the role of medical management has become increasingly recognized, particularly in cases involving asymptomatic patients or those at a high risk for surgical complications. In this review, we aimed to investigate the current guidelines and evidence supporting various medical management strategies for MMD, including the importance of controlling risk factors and judicious use of antithrombotic therapy. Given the considerable variability in patient presentation, such as age of onset, symptomatology, and comorbid conditions, it is crucial to adopt tailored therapeutic approaches that address each patient’s unique characteristics. The existing literature on medical management is limited. However, individualized strategies may effectively mitigate the risk of ischemic events and improve the overall patient outcomes. Further research is essential to develop comprehensive and standardized treatment protocols for medical management of adult patients with MMD. In addition, ongoing trials and efforts to develop disease-modifying agents are discussed.

Keyword

Moyamoya disease; Cerebrovascular disorder; Antithromobotic agents; Risk factor management

Figure

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  Figure 1. De novo development of moyamoya disease in a 51-year-old male who experienced recurrent left hemiparesis. (A) Digital subtraction angiography (DSA) image at the initial presentation showing right middle cerebral artery (MCA) stenosis without evident moyamoya vessels. (B) High-resolution vessel wall magnetic resonance imaging (HR-MRI) demonstrated no evidence of atherosclerotic plaque or arterial dissection in the right MCA but showed luminal narrowing (outer diameter, 2 mm) and circular enhancement (arrowhead). (C) The patient experienced recurrent cerebral infarction 3 months later, and repeat DSA revealed newly developed moyamoya vessels (arrowhead). (D) Perfusion MRI, including arterial spin labeling (ASL) and time-to-peak (TTP) maps, indicated reduced cerebral blood flow and delayed cerebral perfusion, leading to a decision to perform direct bypass surgery.

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  Figure 2. Stroke occurrence in the stenotic segment stabilizes over time. A 42-year-old female with an RNF213 heterozygote carrier, who underwent bypass surgery for a right hemispheric infarct, presented with transient right hemiparesis. Initial transfemoral cerebral angiography (TFCA) showed stenosis only in the right middle cerebral artery (MCA), and transcranial Doppler monitoring detected microembolic signals (TCD MESs). High-resolution vessel wall magnetic resonance imaging (HR-MRI) revealed a circular enhancement in the stenotic segment of the left MCA (arrowhead). The patient was treated with antiplatelet therapy and no further symptoms recurred. Follow-up time-of-flight magnetic resonance angiography (TOF-MRA) showed improvement in stenosis and resolution of the vessel wall enhancement (arrowhead).

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  Figure 3. Intracranial plaque associated with RNF213 variant. A 61-year-old female with an RNF213 variant heterozygous carrier with a family history of moyamoya disease presented with recurrent right hemiparesis. Transfemoral cerebral angiography (TFCA) revealed diffuse stenosis from the left distal internal carotid artery to the proximal middle cerebral artery (MCA) without moyamoya vessels. High-resolution vessel wall magnetic resonance imaging (HR-MRI) of the stenotic segment shows negative remodeling (outer diameter, 1.9 mm) and a plaque with intraplaque hemorrhage (yellow arrow) on the non-enhanced T1-weighted image. The affected area exhibits eccentric enhancement (arrowhead). After treatment with aspirin and high-dose statins, follow-up HR-MRI at 1 year showed improvement in the enhancing plaque and a slight reduction in stenosis (arrowhead).

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  Figure 4. Systemic vasculopathy associated with RNF213 variant. A 39-year-old female with an RNF213 variant heterozygote carrier was diagnosed with asymptomatic moyamoya disease (MMD) after transfemoral cerebral angiography (TFCA) revealed characteristic features of the disease. She had a family history of MMD and premature myocardial infarction, and a relative who died young from the latter. The patient presented with chest pain and was diagnosed with unstable angina. Coronary angiography (CAG) revealed diffuse spastic stenosis suggesting RNF213 variant-related systemic vasculopathy.

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  Figure 5. A substantial improvement in vascular remodeling in patients with moyamoya disease prescribed cilostazol. A 24-year-old female presented with transient sensory changes on the right side. Genetic testing reveals RNF213 heterozygosity, and HR-MRI revealed negative remodeling and circular enhancement. She was prescribed cilostazol (100 mg) twice daily during the study period and underwent serial HR-MRI three times. (A) Time-of-flight magnetic resonance angiography (TOF-MRA) showed improvement in bilateral stenosis of the middle cerebral arteries (MCAs) during the follow-up. Baseline TOF-MRA indicated severe stenosis in the bilateral MCAs; however, only mild stenosis was observed in the left MCA at the last follow-up TOF-MRA. (B) HR-MRI indicated left MCA shrinkage, which improved in follow-up imaging (outer diameter of MCA: 1.10 mm at baseline, 1.55 mm at the intermediate follow-up, and 1.70 mm at the last follow-up). Vascular enhancement was persistently observed in the follow-up images. Reproduced from Kim et al. J Clin Neurol 2022;18:610-618,74 under the terms of Creative Commons (CC-BY-NC) License.

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  Figure 6. Adult moyamoya disease associated with Graves’ disease. A 40-year-old female with ischemic-onset moyamoya disease (MMD) was diagnosed with Graves’ disease and presented with left homonymous hemianopsia. Magnetic resonance images of (A) diffusion-weighted images (DWI), (B) fluid-attenuated inversion recovery (FLAIR), and (C) magnetic resonance angiography (MRA) at onset demonstrate acute cerebral infarction in the right occipital lobe and bilateral internal carotid artery (ICA) terminal stenosis with decreased signal intensity in the bilateral middle and anterior cerebral arteries (MCA and ACA). In light of her previous history of weight loss and hand tremors, she was diagnosed with hyperthyroidism (free T3 8.69 pg/mL, free T4 3.27 ng/dL, undetectable thyroid stimulating hormone [TSH]; and positive anti-TSH receptor antibody and anti-thyroglobulin antibody); thus, she was managed medically with antithyroid therapy with 15 mg/day of methimazole and 15 mg/day of potassium iodide for 2 weeks. (D) MRA after antithyroid therapy (euthyroid state) demonstrated no change in bilateral ICA terminal stenosis. (E and F) Catheter angiography in the euthyroid state confirmed the definitive diagnosis of MMD (carotid angiograms) when (G) iodine-123 metaiodobenzylguanidine single-photon emission computed tomography (IMP SPECT) delineated a marked hemodynamic compromise in the affected hemisphere, suggesting surgical revascularization in the right hemisphere. The patient then underwent revascularization surgery in a euthyroid state, without complications. (H-J) Intraoperative view of the right superficial temporal artery (STA)-MCA bypass. (H and I) The M4 segment of the right MCA is explored, and the stump of the right STA is anastomosed. (J) Indocyanine green videoangiography demonstrating an apparent patent STA-MCA bypass. (K) MRA performed 2 days after revascularization demonstrated patent STA-MCA bypass with thick high signal intensity (arrow). (L) IMP SPECT performed 1 day after revascularization indicated hemodynamic improvement in the right hemisphere.

Reference

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