Overview

Moyamoya disease is a progressive, chronic illness of the brain that is caused by the narrowing of blood vessels, leading to artery blockages at the basal ganglia point of the brain.^1,2 This can cause various types of strokes in the body, including haemorrhagic or ischaemic strokes. It can be an inherited condition or appear as an isolated disease with no obvious trigger or cause. Moyamoya disease typically affects children and people of around 40 years of age, people assigned female at birth, and those of Asian heritage. The term “moyamoya” is a Japanese term for a puff of smoke which mirrors the appearance of the blood vessels.²

Signs of Moyamoya disease

Moyamoya disease has various symptoms that vary with age groups, including:³

• Headache
• Weakness or numbness, commonly on only one side of the body
• Vision changes
• Involuntary movements
• Cognitive impairments, including trouble with memory or focus

In children, recurring transient ischaemic attacks occur, as well as seizures and difficulty in performing cognitive functions, such as recalling memories.^2,4 Adult patients experience more haemorrhagic strokes than younger patients. Ischaemic events are the most significant symptoms for moyamoya disease.⁴ Strokes play a huge part in the progression of the disease, as they exacerbate the underlying vasculopathy and neurological deterioration. The diagnosis of this disease typically involves neuroimaging techniques such as magnetic resonance imaging, focusing on the appearance of blood vessels, and magnetic resonance angiogram to see blood flow. Computerised tomography scans are also used to identify any abnormal blood vessels in the head and neck.³

Current treatments & problems with them

Currently, there is no cure for moyamoya disease, however, there are many forms of treatment. The main aim of these treatments is to improve blood flow to the brain to reduce the likelihood of strokes reoccurring and other symptomatic control. 

Revascularisation surgery is used as the standard treatment for preventing the progression of strokes and, therefore, the disease. This surgery aims to increase intracranial blood flow through the external carotid arteries, which are the major blood vessels in the neck that supply blood to the brain. This is done through direct bypass, being the surgical connection between an artery outside the skull and an artery inside the skull, or via pial synangiosis, where a blood-rich tissue is in contact with the surface of the brain. Revascularisation surgery has been used to prevent ischaemic strokes and further haemorrhages.⁵

Despite revascularisation being successful, it also comes with risks and complications. It can cause hyperperfusion syndrome and epilepsy due to haemodynamic irregularities. Neurological rehabilitation is used in treating vascular cognitive impairment which is caused by moyamoya disease. Studies showed that specific motor and neuropsychological rehabilitative treatments were effective with patients.⁶ Antiplatelet therapy has shown potential benefits in treating moyamoya disease and is therefore being researched further.

Role of Antiplatelet therapy

Antiplatelet therapy has been used in patients with all stages of moyamoya disease, however, there is limited evidence on its treatment ability. Blood is largely made up of red and white blood cells, as well as platelets (smaller red blood cells which form blood clots when the body has an injury).⁷ Platelets play a vital role in haemostasis, which is a process that repairs injured blood vessels. Typically, antiplatelet drugs work by targeting the major steps in primary haemostasis, which are platelet adhesion, activation and aggregation. When the body undergoes an injury and a blood vessel is damaged, platelets stick to the exposed endothelial surface, which consists of collagen and the Von Willebrand factor. This is achieved through the interaction of these with various glycoproteins. These platelets subsequently undergo a shape change, become activated, and release substances that stick to more platelets. This continuous aggregation forms a clot through the binding of fibrinogen and Von Willebrand factor to the activated glycoproteins on the platelet surface.⁸

In moyamoya disease, antiplatelet drugs work through their ability to prevent the formation of blood clots, through stopping platelets from sticking together, which can cause strokes and heart attacks. When there is excessive platelet aggregation, ischaemic events are increased because the blood vessels are further obstructed, further restricting blood flow to the brain.⁷

Despite these drugs theoretically being effective, five studies have assessed the risk of ischaemic stroke in the follow-up period and have shown no evidence to support a reduced risk of these events. However, three studies showed a reduced risk of haemorrhagic strokes when compared to a patient group not using antiplatelet therapies.⁹ Studies also showed that the patency bypass (when blood vessels are unobstructed and blood is able to pass through) had improved. A different study also demonstrated a decreased rate of mortality and higher survival rates.¹⁰

Clinical Efficacy of Antiplatelet therapy

Through investigation, it was found that antiplatelet therapy could not prevent recurrent ischaemic strokes. This has been further supported by a 10-year follow up evaluation demonstrating that antiplatelet therapy did not affect the rate of blood flow in the brain. There is some research which shows the drug cilostazol improves cerebral blood flow and cognition better than other antiplatelet drugs for ischaemic moyamoya patients.⁵

In a study which compared antiplatelet and surgical treatments in ischaemic moyamoya patients, the ischemic strokes were the lowest in patients who underwent revascularisation surgery. This means that antiplatelet therapy is not only ineffective in treating ischemic events, but is also less effective than using revascularisation surgery as a treatment option.¹⁰

Considerations of Antiplatelet therapy

When analysing the statistics named above in terms of effectiveness, the prior treatments of moyamoya disease should be considered. Revascularisation surgery affects the results. Some studies also show that moyamoya disease progresses gradually in non-Asian ethnicities, therefore, the subgroup analysis should be performed based on particular ethnicities. A major risk when using antiplatelet therapies is excessive bleeding from a lack of blood clots.⁷ These drugs prevent all clots with no selectivity, meaning even those that are required after injuries are prevented. Antiplatelet therapies also come with numerous side effects including:⁷

• Shortness of breath
• Disturbed menstrual periods
• Bruises
• Haemorrhages
• Gastrointestinal bleeding
• Nausea

When performing antiplatelet therapy on patients, a number of aspects need to be considered: including administration, dosage, duration of therapy and patient suitability. Depending on the patient’s needs and preferences, these antiplatelet drugs can be administered via oral, intravenous or rectal routes.¹¹ It is usually recommended that a patient has a low dosage of the drug over a long-term period.¹² Before a patient starts antiplatelet therapy, they should have a risk assessment on their potential to excessively bleed, due to the potential genetic and sex-related factors. Additionally, people who are planning to have surgery or who possess any bleeding problems should not take these drugs, due to the risks that are associated with them.¹¹

FAQs

How is moyamoya disease prevented?

Unfortunately, there are no known ways of preventing moyamoya disease, due to the genetic and age related links. However, when the symptoms are recognised early, surgical treatment can slow the disease’s progression and reduce symptoms.¹³

How does moyamoya disease affect the quality of life for patients?

Without effective treatment, patients with moyamoya disease may experience escalating or progressive strokes, fatal haemorrhages and even mental decline, leading to a decreased quality of life. However, with effective treatment, patients can live a relatively healthy and normal life. As moyamoya disease is a progressive disease, the earlier it is recognised and treated, the higher the chances are of survival and living a normal life. Therefore, a doctor should be consulted as soon as symptoms appear.³

How likely am I to be diagnosed with moyamoya disease?

Moyamoya disease affects approximately 5 in 100,000 people and is therefore a rare disease. It is more common in Asian populations, but ten times less common in Europe. It is also twice as common in people assigned female at birth than in people assigned male at birth.¹⁴

Summary

While antiplatelet therapy is still being researched, its results are promising for patients with certain symptoms. Despite its ineffectiveness in treating and preventing ischaemic events, it has proven effective with haemorrhagic events and has improved patency, bypass and overall survival rates. To be able to study the success of antiplatelet therapy further in moyamoya disease, a larger and more diverse group of patients need to be explored to gain broader results. Through more research into the genetic reasons contributing to moyamoya disease, more effective treatments may be found.