Introduction

What is moyamoya disease?

Moyamoya disease (MMD) is a rare, chronic disorder of the cerebrovascular system. Diseases that fall under this term involve a disruption to the blood flow in the brain. 

MMD is characterised by progressive narrowing of certain arteries in the brain. The scientific term for this closing of blood vessels is ‘stenosis’ or ‘occlusion’.¹ 

MMD specifically affects the following arteries in the brain:

• Internal carotid artery (ICA) – this is one of the two branches of the common carotid artery (CCA)
• Anterior carotid artery (ACA) – this is a branch of the internal carotid artery
• Middle carotid artery (MCA) – this is also a branch of the internal carotid artery²

What happens in moyamoya disease?

The precise mechanism through which arteries in the brain become narrow is unclear. Unlike angina, MMD is non-atherosclerotic, in other words, the occlusion of blood vessels is not attributable to the buildup of fatty substances in the artery walls.

Formation of collateral networks

The narrowing of arteries in MMD can result in the formation of an extensive network of collateral vessels in the brain.³ These vessels are connected to the more central ones and provide an alternative blood circulation route if other arteries become blocked. These collateral networks are often referred to as ‘backup’ blood vessels.

Inflammation and autoimmunity

Chronic inflammation is thought to contribute to MMD. Damage to blood vessels can cause microthrombi to develop. These small blood clots form and attach to the interior walls of blood vessels. This causes narrowing and blockage of blood vessels, potentially resulting in strokes or seizures.

Autoimmune conditions encompass those that involve the immune system mounting an attack against its own healthy cells to cause a range of symptoms. They are a common comorbidity in MMD, particularly type 1 diabetes, Graves’ disease, and thrombocytopenia. Research suggests that MMD occurs due to an abnormal expression of immune proteins. If you have MMD, you may have a high level of autoantibodies, which is a hallmark feature of autoimmunity.⁴

Symptoms and clinical presentation - what’s the difference?

Although these terms are used interchangeably, they do have very different meanings. The former of these terms represent the features associated with a disease that is apparent to you as the patient. For example, chest pain is a common symptom of heart failure because you experience this sensation.

On the other hand, the clinical presentation, or signs, of a disease are indicators usually noted by the healthcare professional and can aid in diagnosing a condition. For example, a sign of heart failure would be an irregular heart rate since this would typically be noted in an ECG to record your heart rate.⁵

Symptoms of moyamoya disease

The following list of MMD symptoms is universal across most age groups. Decreased flow of blood to arteries in the brain is likely causative of these symptoms.

• Headache
• Seizures
• Cognitive impairment and dementia – the latter is particularly common in adults^1,6

Clinical presentation of moyamoya disease

The frequency of the clinical presentation of MMD in paediatrics and adults differs and will be discussed in turn below. 

Paediatrics

Ischemic events

This is the most common clinical presentation in children and adolescents and includes ischemic strokes and transient ischemic attacks (TIAs).¹ Ischemic events occur in 73.9-97.5% of cases. 

Haemorrhagic strokes

These are rare, appearing in only 2.5-8.0% of cases.

Movement disorders

This could include chorea, dystonia, ataxia, and myoclonus, but is relatively uncommon in paediatrics (3.0-4.0% of cases only). Movement disorders are even rarer in adults with MMD.

Other

Developmental delays, learning disabilities, and behavioural changes are also noticeable in this age group.

Adults

Ischemic events

Compared to the paediatric population, these are less common and present in 57.7-70.0% of patients with MMD.

Haemorrhagic strokes

This includes intracranial bleeding which is prevalent in 19.1-42.3% of the adult population, a significantly higher proportion than children and adolescents with MMD.^6,7

FAQs

Who is more likely to be affected by MMD?

MMD is most prevalent in the East Asian population, especially those of Japanese, Korean, or Chinese descent. Also, women are more likely to be affected than men. The main age ranges for the onset of MMD are 5-9 years and 45-49 years. Most cases of MMD are sporadic, albeit 10-15% of cases involve a familial link, suggesting a genetic predisposition to the disease.^1,8

How common is MMD?

Data estimates that the prevalence of MMD in the Nanjing population of China was 3.92 per 100,000 individuals in 2007. In Korea, this value was at 16.1 per 100,000 individuals in 2011.⁸ 

How is MMD diagnosed?

Digital subtraction angiography is the main method of diagnosing MMD. It uses X-rays and a special dye to analyse the flow of blood through the brain, as well as identify any abnormalities in the blood vessels.⁶

A cerebral blood flow study using positron emission tomography (PET) can identify areas in the brain where the passage of blood might be disrupted, indicating the presence of MMD.⁸

Histopathology refers to the examination of body tissues under a microscope and may be useful in the context of MMD by revealing changes in the structure of arteries in the brain.¹

How is MMD treated?

Aspirin helps to prevent strokes in MMD. Alternatively, clopidogrel or cilostazol may be used if aspirin is ineffective. These are anti-platelet drugs and work by stopping platelets, which are a type of blood cell, from sticking together, thereby reducing the formation of a clot which is causative of a stroke.^1,6

However, surgical revascularisation is considered the most effective treatment for MMD because it aims to repair blood vessels in the brain, thus lowering the risk of stroke and bleeding in ischemic and haemorrhagic MMD, respectively.¹

Direct revascularisation includes a bypass between the superficial temporal artery and the middle carotid artery (STA-MCA bypass). This has been shown to reduce bleeding⁹ and relieve severe headaches too,¹⁰ owing to improved blood flow in the brain.

Conversely, indirect vascularisation involves placing a section of vascularised tissue over the brain surface, allowing new blood vessels to form.¹ Research has shown that this type of surgery is successful for stroke prevention in paediatric MMD patients.¹¹

What is the prognosis for MMD?

You are likely to notice the progression of your symptoms over a period of several years with events like a stroke leading to neurological complications, which can severely affect your quality of life. Early surgical intervention generally results in a better prognosis.¹² 

Summary

MMD is a condition that affects the arteries in the brain to causes symptoms like headache and seizures, as well as stroke and haemorrhage as a result of the narrowing of these blood vessels. Clinical presentation differs between the paediatric and adult populations, with ischemic events more common in children while adults are more likely to experience haemorrhagic stroke. MMD usually affects the East Asian population albeit the condition is rare. Angiography is the primary diagnostic method and surgical revascularisation is usually the first approach to treating MMD.