Overview

Miller Fisher syndrome is a rare clinical variant of Guillain-Barré Syndrome and accounts for approximately 5-10% of all cases of Guillain-Barré Syndrome.¹ Miller Fisher syndrome is an acquired nerve disease which primarily affects the peripheral nervous system, which includes the nerves outside of the brain and spinal cord. Miller Fisher syndrome affects both children and adults, and it typically occurs up to four weeks after a bacterial or viral infection.

It is an autoimmune condition whereby the patient’s immune system attacks their own nerve cells due to mistaking them as foreign matter.

There is treatment available, however, most patients recover within six months even without treatment. Miller Fisher syndrome is very rarely life threatening, and very few patients report permanent neurological issues or relapse.²

Classic triad of symptoms

Miller Fisher syndrome usually presents with at least two of the following symptoms: ophthalmoplegia, ataxia and areflexia.³

Ophthalmoplegia 

Ophthalmoplegia is the paralysis of the eye muscles. There are two types of ophthalmoplegia: external and internal.

External ophthalmoplegia is the paralysis of the voluntary extraocular muscles, which are needed for eye movement, whereas internal ophthalmoplegia is the paralysis of the muscles involved in pupil constriction and lens adjustment.⁴

Both external and internal ophthalmoplegia may occur in Miller Fisher syndrome, although external ophthalmoplegia is more common - external ophthalmoplegia occurs in all patients with Miller Fisher syndrome, and internal ophthalmoplegia presents in approximately half of Miller Fisher syndrome cases.⁵

Ataxia

Ataxia is a collection of disorders which affect coordination, balance and speech. People with ataxia may struggle with balance, speaking, swallowing, writing, eating and vision. Miller Fisher syndrome causes acquired ataxia due to the autoimmune attack of the peripheral nervous system. When the nerves involved in proprioception - the process of sensing the body’s own position and movements - are attacked by Anti-GQ1b antibodies, motor coordination is impaired, so signs of ataxia can be observed as difficulty balancing, speaking, etc.

Areflexia

The term areflexia describes a state where the muscles are unresponsive to stimuli, so reflex responses are absent.⁶

Examples of absent reflexes include:

• Patellar (knee-jerk) reflex
• Achilles (ankle-jerk) reflex
• Biceps and triceps reflexes in the upper limbs⁷

Again, this is due to damage to the peripheral nerves. The damage impedes the reflex arc so the muscles don’t receive the signal to contract, or the signal is weakened.

Additional clinical features

Sensory symptoms

Paresthesia - A ‘pins and needles’ sensation may be experienced, most commonly in the hands and feet.

Numbness - A loss of sensation, usually experienced in the extremities such as the fingers or toes.

Pain - Neuropathic pain may occur due to the damage and inflammation of the peripheral nerves

Sensory symptoms in Miller Fisher syndrome tend to be symmetrical, meaning both sides of the body are affected.⁸

Motor symptoms

Muscle weakness can affect various parts of the body in Miller Fisher syndrome, especially the eyes, face and limbs.⁹

Muscle weakness in the eyes (ophthalmoplegia) can cause double vision (diplopia), drooping eyelids (ptosis) and difficulty moving the eyes in different directions.

Facial muscle weakness impairs facial expressions, speech and eating.

Weakness of the limbs impairs movement, making tasks like walking or lifting objects difficult.

Autonomic dysfunction

The autonomic nervous system controls involuntary bodily functions such as blood pressure, thermoregulation and digestion. Autonomic dysfunction is less common in Miller Fisher syndrome than in other Guillan-Barre variants, however, it may still occur and impact patient outcomes if the autonomic nerves are damaged.¹⁰

Autonomic Dysfunction may cause cardiovascular issues, including:

Orthostatic hypotension -  A sudden drop in blood pressure when standing, causing dizziness and/or fainting.

Arrhythmias - Irregular heartbeats, either too fast (tachycardia) or too slow (bradycardia).

Blood pressure variations: Fluctuations in blood pressure occurring spontaneously - not due to changes in activity or posture

Autonomic Dysfunction can also cause gastrointestinal issues, including:

Gastroparesis - Delayed gastric emptying due to food passing through the stomach at a slower rate than normal, resulting in nausea, vomiting, and bloating.

Constipation or diarrhea: Abnormal bowel movements due to disrupted autonomic control of the gastrointestinal tract.

Autonomic Dysfunction might impair an individual’s ability to regulate their own internal body temperature (thermoregulation). Ordinarily, a person’s internal body temperature is 37°C, however, someone with Miller Fisher syndrome may have an internal body temperature which deviates from this. This can cause 

Hyperhidrosis: Excessive sweating.

Anhidrosis: Lack of sweating, exacerbating difficulties in temperature regulation as affected individuals struggle to cool down.

Diagnostic procedures

There is no definitive test to confirm Miller Fisher syndrome, however, there are multiple tests a healthcare provider can perform to suggest or eliminate the possibility of Miller Fisher syndrome. (Cleveland Clinic)

Clinical examination

Healthcare providers may perform a clinical examination to identify the symptom triad associated with Miller Fisher syndrome.

Eye movement can be assessed by asking the patient to follow a penlight in different directions with their eyes.

A patient history may also be taken whereby the patient is asked about any complaints of double vision, difficulty focusing, or eyelid drooping.¹¹

Ataxia can also be assessed through observational assessment, involving a series of tests to evaluate gait, balance, and coordination. A healthcare provider will assess the individual’s gait by asking the individual to walk normally and then on their toes/heels, looking for signs such as an unsteady gait characterised by swaying and irregular foot placement.

Tests such as brain imaging, blood tests and genetic testing will be conducted to determine if there is an underlying cause, other than Miller Fisher syndrome, which may be causing the ataxia.¹²

Pronator Drift Test: The patient extends their arms forward with their palms facing up and eyes closed. It’s observed whether one arm drifts downward or pronates, indicating possible cerebellar or proprioceptive dysfunction.¹³

Areflexia is also a diagnostic indicator of Miller Fisher syndrome. Typically, a reflex hammer is used to test deep tendon reflexes at various sites (e.g., knees, ankles, biceps, triceps).¹⁴ Responses on both sides of the body are observed to detect symmetry.

Laboratory and imaging studies

Lumbar puncture - a sample of the fluid surrounding the spine (cerebrospinal fluid) is removed and analysed for Anti-GQ1b antibodies. These are the antibodies which damage nerve cell membranes, leading to the nerve damage characteristic of Miller Fisher syndrome. The presence of anti-GQ1b antibodies is highly specific for Miller Fisher syndrome and some related conditions within the spectrum of Guillain-Barré syndrome. A positive result strongly supports the diagnosis of Miller Fisher syndrome, however, a negative result does not completely eliminate the possibility of Miller Fisher syndrome, though it may prompt consideration of other diagnoses and further testing.¹⁵

Nerve conduction studies - These measure how quickly an electrical signal travels through the nerves. The results usually differ from nerve conduction studies of healthy people due to nerve damage. Typical findings in a Miller Fisher syndrome patient are:

Slowed Conduction Velocities: Reduced speed of electrical transmission along the nerves, indicating demyelination or nerve damage.

Prolonged Latencies: Delayed response times from nerve stimulation to muscle action (in motor nerves), reflecting impaired nerve function.¹⁶

Imaging techniques - CT and MRI scans are not the primary diagnostic tools for Miller Fisher syndrome, however, they play an important role in the diagnostic process by excluding other potential causes of the patient's symptoms such as strokes, tumors, or structural abnormalities in the brain and spinal cord.¹⁷

FAQs

Is miller-fisher syndrome contagious?

Miller Fisher syndrome is not contagious, so it doesn’t spread from person to person.

Is miller-fisher syndrome hereditary?

MFS can be inherited, however, it’s rare for two people in the same family to have the disorder.

What causes miller-fisher syndrome?

MFS is an autoimmune condition where the body's immune system mistakenly attacks its own nerves. This often occurs after a respiratory or gastrointestinal infection caused by a bacterium or virus.

How common is miller-fisher syndrome?

MFS is a rare condition. It accounts for approximately 5-10% of all cases of Guillain-Barré Syndrome.

Are there any long-term complications associated with miller-fisher syndrome?

Most patients recover fully from MFS without long-term complications. However, some patients experience residual symptoms, including mild ataxia, persistent weakness, or sensory issues.

Can miller-fisher syndrome recur?

Recurrence of MFS is rare, but it can happen. Some patients may experience a relapse of symptoms or a new episode after the initial recovery. Monitoring and early intervention in case of recurrence are essential to manage the condition effectively.

Summary- miller fisher syndrome (MFS)

Miller Fisher syndrome is a rare variant of Guillain-Barré Syndrome (GBS) that affects the peripheral nervous system. It typically follows a bacterial or viral infection and is an autoimmune disorder where the immune system attacks the body's nerves. The condition usually presents with a classic triad of symptoms: ophthalmoplegia (eye muscle paralysis), ataxia (coordination issues), and areflexia (absent reflexes).

Other symptoms may include sensory issues (paresthesia, numbness, and neuropathic pain), motor symptoms (muscle weakness in eyes, face, and limbs), and possible autonomic dysfunction (cardiovascular and gastrointestinal problems).

Diagnosis involves clinical examination, nerve conduction studies, lumbar puncture to check for Anti-GQ1b antibodies, and imaging tests to rule out other conditions.

Most patients recover within six months, with rare long-term complications, though recurrence is possible. The condition is not hereditary or contagious.