Moyamoya disease (MMD) is a rare, progressive cerebrovascular disorder in which there is a gradual narrowing or occlusion of the terminal portions of the internal carotid arteries (arteriae carotides internae) and adjacent cerebral arteries. As a result, the blood supply to the brain becomes restricted. In response, the body forms fine compensatory vessels, known as collateral vessels, to maintain oxygen supply to the brain. In vascular imaging, these networks of vessels appear like a cloud of smoke, which gave the disease its name: “Moyamoya” means “smoke cloud” in Japanese (see Figure). The disease was first described in Japan in 1957 and was defined as an independent disease entity in 1969 by the neurosurgeon and physician-scientist Jirō Suzuki and his colleague Akira Takaku.

For a long time, Moyamoya disease was considered a condition occurring almost exclusively in East Asia. Today, it is known that it can occur worldwide, although there are significant geographical differences. Japan has the most extensive epidemiological data available. There, incidence rates between 0.35 and 0.94 cases per 100,000 inhabitants per year have been reported. Earlier studies estimated the prevalence at approximately 3.16 cases per 100,000 inhabitants, while later surveys reported an increase to around 10.5 cases per 100,000 inhabitants. This increase is probably not explained solely by a true rise in disease occurrence but is also likely related to improved diagnostic capabilities, particularly the increasing use of magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and greater awareness of the disease.

Other East Asian countries also show a significantly higher disease burden compared with Western regions. In South Korea, a prevalence of approximately 16.1 cases per 100,000 inhabitants has been reported, making it one of the countries with the highest known prevalence worldwide. In China, the estimated prevalence is around 3.92 cases per 100,000 inhabitants. These differences between Asian countries may be influenced by genetic factors, varying diagnostic criteria, healthcare systems, and the availability of epidemiological data.

In contrast, Moyamoya disease is considerably rarer in Europe and North America. A population-based study from California and Washington State investigated 298 patients and determined an incidence of 0.086 cases per 100,000 inhabitants. Another analysis based on a national US hospital database showed higher values of approximately 0.57 cases per 100,000 inhabitants. For Washington State and California, a prevalence of approximately 2.2 cases per 100,000 inhabitants has been described. Despite the lower frequency of the disease in Western countries, recent studies indicate an increasing number of diagnosed cases, which is likely explained by advances in imaging techniques and improved detection of milder disease courses.

The exact cause of Moyamoya disease has not yet been fully clarified. However, genetic predisposition plays a central role. The RNF213 gene is considered the most important risk factor, particularly among East Asian patients. The p.R4810K variant occurs frequently in affected individuals from Japan, Korea, and China, whereas other rarer genetic alterations are more commonly identified in European and North American patients. In addition, other genes such as DIAPH1 have been associated with the disease. Current research approaches using modern methods such as induced pluripotent stem cells (iPSCs) and CRISPR gene editing are investigating how these genetic changes influence vascular development and may contribute to the development of new treatment options.

Symptoms arise due to progressive cerebral hypoperfusion or bleeding from the fragile collateral vessels. Typical symptoms include strokes, headaches, seizures, and cognitive impairments. Especially in children, repeated episodes of reduced blood flow can lead to long-term neurological developmental disorders. In adults, the risk of intracranial hemorrhage is more prominent, as the newly formed vessels are structurally unstable.

Diagnosis is primarily based on imaging techniques. Digital subtraction angiography (DSA) is considered the gold standard, as it allows visualization of the typical arterial narrowing and characteristic collateral vessel formation. The Suzuki staging system describes disease progression based on increasing vascular stenosis and the development of collateral vessels.

In the early stages (stages 1–3), important blood vessels at the end of the internal carotid artery progressively narrow and become occluded. Subsequently, the body forms the characteristic Moyamoya vessels. In later stages (stages 4–5), additional collateral connections develop between vessels of the external carotid artery and intracranial vessels. As a result, the typical Moyamoya vascular network gradually decreases.

In addition, MRI and magnetic resonance angiography (MRA) play an important role in detecting cerebral infarctions, impaired blood flow, and characteristic findings such as the so-called “ivy sign.” Perfusion studies such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), or MR perfusion imaging additionally allow assessment of cerebral blood flow and vascular reserve capacity.

Currently, there is no medical therapy that eliminates the underlying cause of the disease. Medications such as acetylsalicylic acid (aspirin, ASA) may be used to reduce the risk of ischemic strokes. Stronger anticoagulants are generally avoided because of the increased risk of bleeding. Therefore, the most important treatment is surgical revascularization (the restoration of blood supply to a tissue).

The aim of surgery is to create new blood pathways to the brain and thereby improve cerebral perfusion permanently. A distinction is made between direct and indirect bypass surgery. In direct revascularization, a branch of the superficial temporal artery (arteria temporalis superficialis) is directly connected to a cerebral artery, allowing immediate additional blood flow to the affected brain tissue. This procedure is particularly preferred in adults.

In children, the indirect method is more commonly used. In this approach, well-vascularized tissue is placed onto the surface of the brain, allowing new blood vessels to develop gradually over time. Frequently, both methods are combined.

After treatment, regular follow-up examinations using MRI, MRA, and perfusion imaging are necessary to evaluate bypass function and the development of cerebral blood flow. Careful blood pressure management is also essential, as both excessively high blood pressure increases the risk of hemorrhage, while excessively low blood pressure can worsen cerebral perfusion.

In summary, Moyamoya disease is a rare but complex cerebrovascular disorder with a distinctive geographical distribution. Although the exact causes are not yet fully understood, modern diagnostic methods now allow earlier detection. Surgical revascularization currently represents the most important treatment option to improve cerebral blood flow and prevent severe neurological complications. Future genetic and molecular research may lead to the development of new targeted therapies.

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