Moyamoya disease is a worldwide condition,The same going for Epilepsy.¹ This is because epilepsy affects every age, race, class, and geographical location.⁵ The difference is that Moyamoya disease affects more of the Japanese female population.¹

While Moyamoya earned a nickname, epilepsy has been a stigmatised condition.¹ Long ago, epilepsy was associated with evil spirits, when in reality it's a common neurological condition.^4,5

Seizures occur in 20-30% of all cases of Moyamoya disease.³ When the seizures become recurring, it earns the name, symptomatic locally related epilepsy.⁷ Epilepsy in moyamoya disease is common, especially among the child demographic.⁷ Often, moyamoya disease in children has a rapid descent, and it has poor outcomes.¹¹

Understanding moyamoya disease and epilepsy

What is moyamoya disease?

In 1957, Takeuchi and Shimizu discovered Moymoya disease (MMD). It was described as hypoplasia of the bilateral internal carotid arteries. Over the years, this description has evolved. Today, it is a chronic occlusive cerebrovascular condition.¹ It involves two events:²

• A continuous narrowing of the end part of the carotid artery
• And an unusual blood vessel network at the base of the brain

Ischemic attacks and intracranial haemorrhage, also known as a brain bleed, are some characteristic features of the disease. Although ischemic attacks are common among children, adults may have both features.³ Although it can affect all age groups,¹ the majority remains in 5-year-olds and 40-year-olds.³ 

What is epilepsy?

The term epilepsy describes a group of disorders associated with epileptic seizures.⁴ These seizures must happen without an offence to the central nervous system or because of:⁵

• Neurobiological
• Cognitive
• Psychological, or 
• Social seizure recurrence

Epilepsy tends to affect men more than women.⁵ Also, it is more common with the elderly. This trend accounts for the high rates of the following diseases found in the age bracket:⁵

• Stroke
• Neurodegenerative disease
• Tumours

Does moyamoya disease cause epilepsy?

In moyamoya disease, there are two compulsory events:⁷  

• Ischemic attacks
• Intracranial haemorrhage

Outside of these, epilepsy follows right behind.⁷ Epilepsy, stroke, and neurological deficits can present in both children and adults.³ Epilepsy occurs more in children,⁶ especially among those three years of age or younger.⁷

Both stroke and epilepsy in moyamoya disease are identical twins. This is because they occur alike in their clinical signs, symptoms, and how they develop.⁷

The causes of epilepsy in this moyamoya disease are as follows:^6,7

• Stroke after ischaemic attack
• Stroke after a hemorrhagic attack 
• Postoperative hyperperfusion: increased blood flow to the brain
• Cortical ischemia

What are the risk factors for epilepsy in moyamoya disease?

Epilepsy in this condition is a type of post-stroke epilepsy.⁷ The risk factors for post-stroke seizures include the following:⁷

• Cerebral haemorrhage
• Cortical lesion
• Carotid artery stroke
• Occurrence of post-stroke bacterial infection

What Causes Moyamoya Disease?

The cause of moyamoya disease is unknown. But some risk factors that can increase vulnerability, including:^2,5,8

• Presence of chromosome 17 — as it is a carrier of the MMD gene, particularly for East Asians
• Female gender
• Hereditary conditions like neurofibromatosis, Down syndrome, sickle cell anaemia, and collagen vascular disease
• Inflammatory conditions
• Cranial irradiation

What are the symptoms of moyamoya disease?

When it comes to moyamoya diseases, symptoms vary with age.² Although it generally presents with the following signs and symptoms:^2,9

• Ischaemic stroke
• Seizure
• Headache
• Visual and cognitive impairment
• Disturbed consciousness
• Involuntary movement

Often, children have a stroke or recurring transient ischemic attack (TIA) as a first symptom.⁷ TIA usually comes with either muscle weakness or hemiparesis.⁷ While adults may have TIA due to blocked arteries, hemorrhagic strokes are more common.⁷ They occur because of bleeding into the brain.⁷

Other symptoms particular to children often occur after events like:¹

• Crying
• Blowing on hot noodles
• Or playing the harmonica

This is because the activities lead to hyperventilation, being abnormal breathing. The narrowing of the cerebral arteries, before the following symptoms occur:¹

• Headache
• Involuntary movement 
• Convulsive seizures

How does moyamoya disease develop?

When it was discovered in 1957, Suzuki and Takaku identified its developmental stages. These stages are:¹

• Narrowing of the carotid syphon
• Initiation
• Intensification
• Minimisation
• Reduction
• Disappearance of Moyamoya vessels

Although the true path of development is unknown, we know a few facts. There are:^2,3,8

• Chromosome 17 plays a role in disease, but the exact mechanism is not confirmed
• There is rapid growth of new epithelial and smooth muscles. This results in blockage and clear but abnormal angiogenesis
• It involves intimal hyperplasia and medial thinness
• Affected vessels are wide penetrating arteries with fibrin deposits on their walls. They have fragmented elastic laminae, weakened media, and there is the formation of microaneurysms
• Cortical mircovascularization occurs as a compensatory mechanism due to reduced cerebral blood flow. They could also result from abnormal neovascularization due to vascular occlusion
• During active compensation, there is enough haemodynamic impairment. Once present, cortical neovascularization occurs and active compensation begins

How is moyamoya disease diagnosed? 

The exact cause of moyamoya disease is unknown. This is why diseases with similar angiogenic findings have to be ruled out. Diseases like:¹

• Atherosclerosis
• Autoimmune disorders
• Meningitis
• Brain tumours
• Down syndrome
• Neurofibromatosis
• Head trauma
• Post-radiation state

Using the following diagnostic criteria, moyamoya disease is confirmed:¹ 

• Blockage of the end part of the carotid artery
• Blockage of the proximal parts of the anterior cerebral arteries 
• Blockage of the middle cerebral arteries
• Blockage of the middle and anterior cerebral arteries
• Unusual blood vessel networks in the area of blockage 
• Bilateral involvement

To observe the findings above, doctors make use of the following diagnostic tools:^2,3

• Catheter cerebral angiography
• MRI (Magnetic Resonance Imaging)
• MRA (Magnetic Resonance Angiography)
• CT (computed tomography)
• Electroencephalography

But, catheter cerebral angiography is the benchmark of diagnosis. It reveals the general concept of the disease—the smoky appearance at the base of the skull.³ Catheter cerebral angiography is a criterion in diagnosing moyamoya disease. This is the standard for unilateral cases. In bilateral cases, there are exceptions for MRA or MRI usage. MRI is preferable when looking for ischemic brain lesions, even if they are not symptomatic.²

How is epilepsy diagnosed in moyamoya disease?

A doctor can make a diagnosis of epilepsy based on a detailed history or observation of seizures.⁵ But in moyamoya disease, it is different. Doctors use abnormal findings on electroencephalograms to arrive at a diagnosis. Confirmation of said diagnosis depends on the type of epilepsy.⁷ 

How to treat moyamoya disease?

Medical management of moyamoya disease has two phases:³

• Active phase 
• Chronic phase

The active phase involves the management of acute ischemic stroke. Management in this phase is about symptoms present. This management includes:³

• Intravenous Tissue Plasminogen activator
• Aspirin: It is used for children who develop acute anterior ischemic stroke
• Antiplatelet and anticoagulant
• Antihypertensive if high blood pressure is present

Management during the chronic phase includes:³

• Surgical revascularisation is the priority
• Secondary prevention of stroke: This is done through the use of aspirin or clopidogrel

Surgical management of moyamoya disease involves direct, indirect, or combined revascularization surgeries. It reduces stroke reoccurrences and gives children a better outcome. Surgical procedures include:³

• Direct revascularisation
• Indirect revascularisation
• Combined revascularization

How to treat epilepsy in moyamoya disease?

Management of epilepsy involves the use of anti-epileptic drugs (AEDs). Health professionals tailor AEDS according to the following:¹⁰

• Seizure type
• Epilepsy syndrome
• Other medications currently taken
• Co-morbidity factors
• Age 
• Individuals lifestyle

Management of epilepsy in moyamoya disease does not take the same route. This is because there is no best anticonvulsant to manage attacks. Regardless, drugs like carbamazepine or zonisamide is the first line of treatment. This is because they are effective in treating partial seizures. Phenytoin or valproic acid are also drugs used in the management of epilepsy in moyamoya disease. They are used when there is a low tolerance for carbamazepine or zonisamide.⁷

Summary

Moyamoya disease is a chronic occlusive cerebrovascular condition discovered in 1957. Major events occurring in this disease are ischaemic attack and intracranial haemorrhage. After these events, there is a third, and its name is epilepsy.

Epilepsy in moyamoya disease is prevalent among children three years and older. It is a type of poststroke epilepsy, brought on by several events, one of them being cortical ischemia. Both stroke and epilepsy in moyamoya disease have similarities. These similarities lie in their path of development, as well as their signs and symptoms.

Unlike epilepsy in moyamoya disease, the true cause of Moyamoya disease is still unexplained. Regardless, some factors make people more susceptible to both moyamoya illness and epilepsy in moyamoya disease. The following can make one vulnerable to moyamoya disease: 

• Presence of chromosome 17 - as it is a carrier of the MMD gene, particularly for East Asians
• Female gender
• Hereditary disorders such as neurofibromatosis, Down syndrome, sickle cell anaemia, and collagen vascular disease.
• Inflammatory conditions
• Cranial irradiation

Like the causes, the true path of development is also unknown. Luckily, it is both manageable and diagnosable.