What Is Miller Fisher Syndrome?

Miller Fisher syndrome, named after the physician who described it, is a rare neurological condition that causes weakness of the muscles of the face and upper body. It’s a variant of Guillain-Barré syndrome, which is also an uncommon disease.

Miller Fisher syndrome occurs due to inflammatory demyelination (loss of the protective covering) of the peripheral nerves. The diagnosis of Miller Fisher syndrome involves a clinical examination and diagnostic tests. Immune-modifying treatments can help alleviate symptoms and speed up recovery.

This article describes the symptoms, causes, diagnosis, treatments, and prognosis of Miller Fisher syndrome. 

Types of Miller Fisher Syndrome 

Miller Fisher syndrome is one of several types of neuropathy (nerve diseases). It is a polyneuropathy (involves multiple nerves).

Types of inflammatory demyelinating polyneuropathies include:

• Acute inflammatory demyelinating polyradiculoneuropathy: This conditon involves the nerve roots, which are the large nerves that exit and enter the spinal cord. 
• Acute motor axonal neuropathy: This condition affects the motor nerves. 
• Acute motor and sensory axonal neuropathy: This disorder affects motor and sensory nerves. 
• Chronic inflammatory demyelinating polyneuropathy: This condition causes recurrent demyelination of peripheral nerves, with full or partial recovery between episodes. 

Miller Fisher Syndrome Symptoms 

Miller Fisher syndrome causes muscle weakness. It can affect any muscle in the body, and it most commonly affects the muscles of the face and upper body. 

The symptoms of Miller Fisher syndrome are described as a classic triad, which includes:

• Ophthalmoplegia: Weakness of eye movements can cause blurred vision or double vision. It can look like a lazy eye or uneven eye movements. Sometimes this can cause nystagmus, jerking eye movements when looking toward one side. 
• Ataxia: Balance impairment can affect hand or arm movements, walking, and coordination. 
• Generalized reduced reflexes: Diminished deep tendon reflexes can be detected with a physical examination. This might cause completely absent reflexes or a lower-than-normal reflex response. You might observe this when your healthcare provider checks your patellar reflex by tapping a reflex hammer on your knee.

Other common symptoms of Miller Fisher syndrome include:

• Slurred speech 
• Uneven appearance of the face or eyelids 
• Trouble lifting the arms 
• Difficulty chewing or swallowing
• Choking on food, liquids, or saliva
• Shortness of breath
• Trouble speaking 

Pain is not a typical symptom of Miller Fisher syndrome. Less common symptoms include headaches, loss of taste sensation, and facial weakness appearing after the other symptoms have developed. 

Causes 

Miller Fisher syndrome is caused by inflammation and demyelination of the axonal portion of peripheral nerves. Peripheral nerves are located in the periphery of the body, outside the brain and spinal cord. These nerves run through the limbs, face, and trunk, and they power voluntary and involuntary muscles of the body.

The axons of the peripheral nerves are long structures of the nerves that carry electrical signals through the length of the nerve.

Demyelination is a disease process that causes degeneration of the myelin, which is a type of fat that surrounds the axons of nerves throughout the body. The demyelination that occurs in Miller Fisher syndrome is caused by inflammatory damage.

The trigger for inflammatory demyelination in Miller Fisher syndrome can be idiopathic (without an identifiable cause). Sometimes a mild infection may precede an episode of Miller Fisher syndrome, and it has often been attributed to a dysregulation of the immune system that could be triggered by an infection.

Some of the common infections that may precede Miller Fisher syndrome include:

• The common cold
• Influenza (flu)
• Epstein-Barr virus
• Mononucleosis

Rarely, Miller Fisher syndrome occurs after immunizations. This is believed to occur when the immunization activates a response in the immune system.

Diagnosis 

The diagnosis of Miller Fisher syndrome is based on a history of symptoms and a physical examination. Sometimes diagnostic tests can be helpful, but they do not consistently show changes in Miller Fisher syndrome. 

Tests that may help in the diagnosis of Miller Fisher syndrome include:

• Blood tests: The blood test results that can help identify Miller Fisher syndrome include serum anti-GQ1b antibody, as well as additional antiganglioside antibodies. These laboratory markers are indicators of immune dysregulation that could cause damage to the myelin of the peripheral nerves. These are not routine tests and would generally be ordered only if Miller Fisher syndrome is suspected.
• Magnetic resonance imaging (MRI): Sometimes this diagnostic imaging test shows enlargement of the facial nerve in association with Miller Fisher syndrome. 
• Electromyography (EMG) and nerve conduction velocity (NCV) studies: An examination of the function of the peripheral nerves can identify patterns that are consistent with axonal demyelination.
• Lumbar puncture/spinal tap: This invasive test involves the removal of a sample of cerebrospinal fluid with a needle. It is safe but has a mild risk of complications. With Miller Fisher syndrome, this test may show elevated protein and can be positive for anti-GQ1b IgG and anti-GT1b IgG, which are antibodies reflecting immune dysfunction.
• Muscle biopsy or nerve biopsy: This is an invasive test that requires surgical sampling of the muscle or nerve. This may show evidence of inflammatory demyelination. Because it is invasive, and it might not be helpful, it is not typically used during the diagnostic process of this condition.

Differential Diagnosis

Several other conditions can cause facial weakness or eye-movement weakness, and these must be differentiated from Miller Fisher syndrome.

Other diagnostic considerations include:

• Bell’s palsy: Often idiopathic, Bell’s palsy causes weakness of the face, usually on only one side.
• Myasthenia gravis: An autoimmune disorder that affects the nerve transmission, myasthenia gravis can cause symptoms that primarily affect the eyes or the eyelids, as well as the upper extremities. Testing for myasthenia gravis involves the administration of a Tensilon test. The treatment is distinct from that of Miller Fisher syndrome.
• Multiple sclerosis (MS): This condition is a demyelinating disorder of the brain and spinal cord. It can cause a variety of symptoms, including facial weakness or upper extremity weakness. It requires a different type of treatment than Miller Fisher syndrome. Diagnostic testing can distinguish between MS and Miller Fisher syndrome.
• Progressive supranuclear palsy (PSP): This neurodegenerative movement disorder is associated with progressive dementia. The prognosis is worse than that of Miller Fisher syndrome.

Treatment 

Miller Fisher syndrome can be treated, and it may improve on its own without treatment. The outcome of Miller Fisher syndrome is expected to be good. The condition can resolve with time, and treatment can speed up recovery.

Treating the disease process includes steroids, plasmapheresis (blood plasma exchange), or immunoglobulin therapy. These interventions modify the immune system to help reduce inflammatory damage. With management of the inflammatory process, myelin is expected to be produced by the body, and the nerves are expected to regain function.

In addition to treating the disease process, symptomatic treatment is often necessary.

Symptomatic management can include:

• An eye patch to prevent the discomfort and dizziness that can be caused by double vision or blurred vision
• Pain-relieving medication for managing headaches
• Oxygen supplementation if there is shortness of breath
• Respiratory support if breathing is impaired
• Dietary modification if swallowing is affected
• Physical therapy as needed

Summary

Miller Fisher syndrome is a rare neurological disorder that occurs due to inflammatory demyelination of the axons of the peripheral nerves, primarily of the face and upper extremity. It is considered a variant of Guillain-Barré syndrome, which is also a rare, inflammatory demyelinating disorder of the peripheral nerves.

The condition is often idiopathic (without a cause), but it can occur as a result of dysregulation of the immune system following a brief or mild infection. Diagnosis is based on clinical examination, and some diagnostic tests can be helpful.

Treatment involves immune regulation, such as steroids, immunoglobulin, or plasmapheresis. The outcome is usually good, and Miller Fisher syndrome is not considered to be fatal. However, if breathing is impaired, respiratory support is necessary.