What Is Miller-Fisher Syndrome?

Many medical conditions are named after the physician who first reported them in academic literature. Although the symptoms of Miller-Fisher syndrome (MFS) were first described in 1932, it was a neurologist called Dr Miller Fisher who described the condition as a form of Guillain-Barré syndrome (GBS) in 1956.¹

Like classical GBS, Miller-Fisher syndrome is a polyneuropathy (disorder affecting multiple nerves) that is often preceded by bacterial or viral infection. It typically causes muscle weakness, problems with coordination and an absence of deep tendon reflexes. The pattern of symptoms can help to differentiate MFS from other forms of GBS.¹

Given that there are multiple forms of GBS, it can be difficult to understand what a diagnosis of MFS means for you or a loved one. In this article, we’ll explore how MFS typically presents, how it is diagnosed and treated, and typical outcomes for patients. So, if you’re keen to find out more about this uncommon neurological condition, you’re in the right place.

Overview

Miller-Fisher syndrome (MFS) is a rare form of Guillain-Barré syndrome (GBS). Guillain-Barré syndrome is usually triggered by an infection, causing the immune system to confuse certain surface markers on our nerves with those found on the infecting agent. The body produces antibodies that attack our nerves, resulting in muscle weakness and other neurological symptoms.¹ 

Making a diagnosis of MFS usually involves a combination of examination, lumbar puncture and nerve tests. Blood tests and scans can yield additional information. MFS has a more favourable prognosis when compared with classical GBS, and most patients make a good recovery.¹

Signs and symptoms of miller-fisher syndrome

MFS presents with at least two of the following symptoms:²

• Ataxia (problems with balance and coordination)
• Ophthalmoplegia (weakness or paralysis of the muscles controlling the eyes)
• Areflexia (a lack of deep tendon reflexes).

Other symptoms that can occur include:¹

• Tingling and/or numbness in the hands and feet
• Limb muscle weakness 
• Facial weakness
• Pain
• Visual changes, like double or blurred vision
• Slurred speech

A few patients can experience problems with their breathing or with regulating their heart rate and blood pressure.¹ 

Like classical GBS, Miller-Fisher syndrome is usually preceded by bacterial or viral infection, typically occurring two to four weeks before the onset of neurological symptoms.^{2, 3} Campylobacter jejuni typically causes food poisoning and is the most common bacterial trigger of MFS. Preceding viral respiratory illnesses are common. Other viral triggers include the human immunodeficiency virus (HIV) and the Epstein-Barr virus (EBV).¹ 

Risk factors for miller-fisher syndrome

MFS is more common in people assigned male at birth (AMAB).³,⁴ It can affect people of all ages but is more common in adults in their thirties and fifties.⁴ 

The link between MFS and preceding infection is well understood, as described above. The condition has also been linked to the following:¹

• Heroin use
• The use of certain medications, including isotretinoin and TNF-alpha antagonists
• Autoimmune diseases, such as sarcoidosis and lupus (SLE)
• Hodgkin’s lymphoma
• Recent surgery and/or epidural anaesthesia
• Previous bone marrow transplant

How is miller-fisher syndrome diagnosed?

The clinical features of MFS can overlap with those of other GBS variants and unrelated neurological conditions.¹ Therefore, a careful work-up by your healthcare provider is required in order to ensure an accurate diagnosis. Your team will work to exclude potential mimics of MFS by conducting a range of examinations and tests. 

1. Medical history and examination

If you have neurological symptoms that could suggest a diagnosis of MFS, your healthcare provider will first take a history to explore your symptoms and how they first occurred. They will also ask about your health more generally, any medications you take, your lifestyle and your family history. 

You will also undergo a medical examination, looking for the signs and symptoms that we explored above. 

2. Cerebrospinal fluid (CSF) analysis

Examining a sample of cerebrospinal fluid (fluid which surrounds the brain and spinal cord), obtained via lumbar puncture, can help support a diagnosis of MFS.¹ This is sometimes called a spinal tap. 

In both GBS and MFS, around 90% of people will have high levels of protein in their CSF at the peak of their symptoms, with normal levels of blood cells.¹ However, CSF studies are normal in around 10% of people, whilst others may show a slight increase in blood cell counts. Therefore, it is not possible to make a diagnosis based on CSF analysis alone.¹

3. Tests on nerves and muscles

Nerve conduction studies look to see how well your nerves can transmit electrical signals. Electromyography looks to see how your muscles respond when the nerves that supply them are stimulated. The results of these tests can provide your healthcare team with valuable information that can help differentiate a diagnosis of MFS from other conditions that cause similar symptoms.⁵ You can find out more about these tests here.

4. Blood tests

70-90% of patients with MFS produce anti-GQ1b antibodies, which target a surface marker on nerve cells called GQ1b.¹ Anti-GQ1b antibodies are highly sensitive and specific to MFS. So, their presence can be very helpful in confirming a diagnosis. However, they can also be present in GBS where there is involvement of the muscles controlling the eyes.²

Additional blood tests can help to rule out other illnesses that could be causing your symptoms.¹

5. Imaging

Scans like MRI and CT scans can provide additional information in cases with diagnostic uncertainty.¹

Management of miller-fisher syndrome

Supportive treatment

If you are diagnosed with MFS, you will receive pain medication if you need it. You will likely be looked after in the hospital initially so that your healthcare team can monitor your symptoms, breathing and heart rate. This will also allow them to ensure that you don’t have a more serious form of GBS. Occasionally, patients with MFS require support with their breathing.¹

Intravenous immunoglobulins (IVIG) and plasma exchange

Both these treatments can reduce the length of time you are unwell with MFS. IVIG are antibodies donated by healthy donors that are injected into the bloodstream of a recipient patient. They act to neutralise the effects of the antibodies that are damaging nerves.⁶ In plasma exchange, the liquid part of the blood is replaced using a machine, removing the antibodies that are damaging nerves.⁶

Rehabilitation

Although most people recover from the initial symptoms of MFS within a few weeks, some people will require a period of rehabilitation to return to their usual level of function. Complete recovery can take several months. Rehabilitation will usually involve input from a range of professionals, including physiotherapists and occupational therapists. With the right support, it is unusual for people to experience long-term muscle weakness.¹

FAQs

How common is miller-fisher syndrome?

GBS occurs in 1 or 2 people per 100,000 each year around the world.⁴ MFS represents a small subset of these cases. The proportion of cases that can be defined as Miller-Fisher syndrome varies geographically. In the West, MDS comprises up to 7% of cases of GBS, whereas in East Asia, this can be up to 25%.⁴

What are the complications of miller-fisher syndrome?

Fortunately, MFS has a generally favourable prognosis compared with classical GBS. The fatality rate is low at less than 5%. Around three-quarters of patients will experience fatigue following their illness, and around a third will experience ongoing pain. Serious complications are uncommon and more likely to occur in those who require extended ICU treatment.¹

How can I prevent miller-fisher syndrome?

Given that infections are a known trigger for MFS, the best way to reduce your risk of the condition is by reducing your risk of infection with common bacteria and viruses. You can do this by maintaining good personal hygiene and food hygiene practices. It is also advisable to practise safe sex.¹

Summary

Miller-Fisher Syndrome (MFS) is an uncommon form of Guillain-Barré syndrome (GBS), which causes muscle weakness and other neurological symptoms. It can affect people of all ages and genders but is more common in people AMAB in their thirties and fifties.

MFS is usually triggered by an infection, such as food poisoning or a respiratory illness. The body confuses surface markers on nerve cells with those found on the infective agent, which causes the immune system to produce antibodies that attack nerve cells. 

In addition to taking a thorough history and conducting an examination, your healthcare provider may wish to conduct tests to help ascertain a diagnosis of MFS. Common tests include a spinal tap, nerve tests and blood tests. 

The mainstay of treatment for MFS is with IVIG or plasma exchange, which can both reduce the duration of illness. Supportive care and medical monitoring are also important. Fatigue is common following initial symptoms, and some patients will suffer from ongoing pain. Rehabilitation may be required to make a full recovery. 

Fortunately, most people with MFS make a full recovery, and long-term muscle weakness is rare.