Miller Fisher Syndrome

What is Miller Fisher Syndrome?

Polyneuropathies refer to situations where multiple nerves are not functioning properly. This can be divided into two main categories – axonal and demyelinating. Axonal neuropathies occur when the axons, or the long cables within nerve cells, are damaged or lost due to various diseases. Demyelinating neuropathies happen when Schwann cells, which are cells that support nerve function, don’t interact well with axons.

Schwann cells have several roles in the nervous system. These cells aid in the transmission of nerve impulses along axons, help with nerve development and repair, regulate activity at connections between nerves and muscles, and present antigens (foreign bodies) to T lymphocytes (a type of white blood cell). Demyelinating neuropathies can be caused by toxins, inherited conditions, or immune-related issues, and can be either acute (short-term) or chronic (long-term).

Acute, immune-mediated demyelinating polyneuropathies (AIDPs) are part of a group of disorders known as Guillain-Barre syndrome (GBS), which was identified by French doctors. Within this group, we’re particularly focusing on the Miller Fisher syndrome (MFS), a rare form of GBS. MFS was first found by James Collier in 1932 and described as a combination of three symptoms: ophthalmoplegia (weakness of eye muscles), ataxia (lack of muscle control or coordination), and areflexia (absence of reflexes). The syndrome was later fully characterized in 1956 by Miller Fisher, establishing it as a unique condition within the range of GBS disorders.

What Causes Miller Fisher Syndrome?

Miller Fisher Syndrome (MFS) and Guillain-Barré Syndrome (GBS) are believed to occur due to an abnormal response by the body’s immune system following an infection (like Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus, or HIV). The body mistakenly starts attacking its own peripheral nerves (nerves outside the brain and spinal cord) due to a case of mistaken identity, as it confuses microbial/viral components with nerve components. This is known as ‘molecular mimicry’, and it triggers inflammation, thus causing these illnesses.

About two-thirds of cases of MFS and GBS show prior symptoms of either a respiratory infection or diarrhea, and roughly half occur after an infection of some sort. However, the exact details of how and why this happens aren’t completely understood by scientists. The misguided immune response can target either the covering of the nerve (myelin) or the nerve fiber (axon) itself.

MFS is mainly associated with problems in the third, fourth, and sixth cranial nerves (‘nerves that originate directly from the brain’). But there have been instances where most of the other cranial nerves were involved as well. A typical finding in MFS is the presence of antibodies (proteins produced by the body to fight infections) against something called GQ1b ganglioside as described earlier. Yet, not finding these antibodies doesn’t completely rule out the disease.

Specific drugs (like heroin, suramin, streptokinase, and isotretinoin), use of a group of drugs called TNF-alpha antagonist therapy, having other autoimmune diseases (like systemic lupus, Hodgkin disease, and sarcoidosis), surgery, epidural anesthesia (anesthesia administered in the space around the spinal cord), bone marrow transplant, and vaccinations have all been associated with this disease.

Risk Factors and Frequency for Miller Fisher Syndrome

Guillain-Barré Syndrome (GBS) is a rare medical condition, with only about 1 to 2 out of every 100,000 people developing it worldwide. The Miller Fisher Syndrome (MFS) variant is even more uncommon, affecting only 1 to 2 out of 1,000,000 people. GBS is found more commonly in men than women, with a gender ratio of 2:1, and the average age when the disease first shows up is around 43.6 years.

• GBS occurs globally, with an incidence rate of 1 to 2 in every 100,000 people.
• The MFS variant is very rare, affecting only about 1 to 2 in every 1,000,000 people.
• Men are affected by GBS more than women, with a ratio of about 2:1.
• The average age of onset for the disease is around 43.6 years.
• Asians are more likely to get GBS, with 15% to 25% of GBS cases occurring in this population, compared to only 5% in Western populations.
• In most cases (72%), GBS is preceded by a viral infection, with there typically being a 10-day period between the infection and the onset of neurological symptoms.
• A study found that recurrence of symptoms was more common in patients with MFS and Bickerstaff brainstem encephalitis (BBE) than in those with GBS.

Signs and Symptoms of Miller Fisher Syndrome

Miller Fisher Syndrome (MFS) is often characterized by three main symptoms: sudden weakness in the eye muscles (acute ophthalmoplegia), loss of reflexes (areflexia), and uncoordinated movement (ataxia). These symptoms often follow a previous illness caused by a bacteria or virus. Other symptoms may include numbness or weakness in the extremities, difficulty speaking and seeing, dizziness, and tingling in the arms and legs.

Physical examination usually reveals weakness in the facial muscles, reduced reflexes, and a loss of certain sensations in the extremities. MFS can also affect the autonomic nervous system, which controls functions such as heart rate and blood pressure, causing symptoms like high or low blood pressure or irregular heart rhythms. In advanced cases that haven’t been treated, these problems can become very serious. Interestingly, the reflex that causes your eye to blink when something touches your cornea may also be affected. Symptoms tend to worsen over a period of four weeks or less.

• Sudden weakness in the eye muscles
• Loss of reflexes
• Uncoordinated movement
• Numbness or weakness in the extremities
• Difficulty speaking and seeing
• Dizziness
• Tingling in the arms and legs
• Weakness in the facial muscles
• Reduced reflexes
• Loss of certain sensations in the extremities
• High or low blood pressure
• Irregular heart rhythms
• Affected corneal reflex

Testing for Miller Fisher Syndrome

If your doctor thinks you might have Miller Fisher Syndrome (MFS) or Guillain-Barré Syndrome (GBS), they might recommend a lumbar puncture. This is a procedure where a needle is inserted into your lower back to collect cerebrospinal fluid (CSF), which is the fluid surrounding your brain and spinal cord. Testing this fluid is useful for determining if you have one of these conditions.

A key indicator of MFS or GBS is something called albuminocytologic dissociation. This is a fancy term for a normal cell count but a high protein level in the CSF. This sign is found in about 90% of patients when the disease is at its worst. However, it’s important to note that only half of the patients show this sign when they first become ill, and having a normal protein level doesn’t rule out MFS or GBS. In fact, about 10% of patients with GBS have normal CSF results.

In addition to testing your CSF, your doctor may also perform nerve conduction studies. These tests measure how well and how fast the nerves can send electrical signals. If you have MFS or GBS, the results of these tests can help confirm the diagnosis and even predict how the disease will progress.

If you have MFS, your doctor may also conduct sensory tests and perform CT scans or MRIs. These images can show swelling of the spinal nerve roots and other signs of MFS, such as problems with the parts of your brain that control movement and facial expressions.

Doctors also use something called the Brighton criteria to diagnose GBS and its variants, including MFS. This is a scoring system that takes into account your symptoms, physical exam results, lab tests, and imaging findings. The criteria look at things like limb weakness, absent or decreased reflexes, the course of the disease, and specific results from CSF and nerve conduction studies.

The Brighton criteria have different levels, ranging from level 1 (very certain it’s GBS) to level 4 (it could be GBS, but other options are possible). Your doctor uses these levels to help figure out if you have GBS or a different disease causing your symptoms.

Treatment Options for Miller Fisher Syndrome

MFS, or Miller Fisher Syndrome, is usually addressed with general supportive care, medications for pain, basic help for breathing when necessary, and immune system therapy. Even though steroids have been used in the past for treating MFS and Guillain-Barre Syndrome (GBS), they’re no longer suggested because they have proven ineffective. In fact, they may even slow down recovery from GBS. Steroids are now only recommended if the patient is experiencing certain types of nerve damage or radiating pain.

For severe cases of MFS and GBS, IV immunoglobulin (IVIG) and plasma exchange, treatments that support the immune system, can be helpful. Patients in poor health may not respond differently to either treatment in terms of survival rates, disability, or the duration of needing breathing assistance. The majority of MFS patients don’t need immune therapy given most recover naturally. However, those with severe MFS who are struggling with swallowing and breathing might benefit from IVIG, though there’s limited evidence to support this. Generally, IVIG is preferred because it is more convenient, readily available and has fewer side effects. But, its high cost may put it out of reach for some patients.

Before starting IV immunoglobulin therapy, healthcare providers typically check the patient’s levels of a certain type of antibody, IgA, as those with low levels are more prone to severe allergic reactions.

For patients experiencing pain associated with GBS or MFS, several different medications might be used, including gabapentin, pregabalin, carbamazepine, and amitriptyline. Opioid painkillers should be used carefully due to their potential to suppress breathing and cause side effects like urine retention.

To prevent blood clots in the deep veins (deep vein thrombosis), which can lead to life-threatening lung clots, patients may be given preventive doses of anticoagulants like heparin or enoxaparin, or they may wear special compression stockings.

Additional supportive treatment may be necessary if the patient is experiencing complications related to the body’s automatic (autonomic) functions. For example, a cardiac pacemaker may be needed for patients with a slow heart rate at risk of complete heart block. Nasogastric tubes, which are inserted through the nose, may be required for feeding patients unable to swallow. If the patient cannot urinate, bladder catheterization may be employed, and a bowel regimen may be necessary to help with constipation. It’s also important to start physical therapy early in the illness, and continue it as the patient starts to recover.

Patients with severe GBS or MFS often need to be hospitalized or admitted to an intensive care unit (ICU), especially if they’re having trouble breathing. In severe cases, 20% to 30% of patients might need mechanical help with breathing, and this could involve inserting a breathing tube into the windpipe or even performing a tracheostomy (surgery to create a hole in the windpipe). Monitoring for signs of breathing muscle fatigue – such as fast heart rate, fast/irregular breathing, noticeable use of muscles to aid breathing – is extremely important in these patients.

What else can Miller Fisher Syndrome be?

Millier-Fisher Syndrome (MFS) can sometimes be confused with other disorders that have similar symptoms. Here are a few of them:

• Brainstem (Bickerstaff) encephalitis
• Pharyngeal-cervical-brachial weakness variant of Guillain-Barré Syndrome (GBS)
• Wernicke encephalopathy
• Ocular Myasthenia Gravis
• Lambert Eaton Syndrome
• Multiple Sclerosis
• Sarcoidosis

One significant feature of brainstem encephalitis is hyperreflexia (overactive or overresponsive reflexes) and encephalopathy which is a general term describing a disease affecting the brain. On the other hand, the pharyngeal-cervical-brachial weakness variant of GBS usually involves sudden weakness of throat, neck, and shoulder muscles accompanied by difficulty swallowing and facial muscle weakness. It’s also important to mention that all three disorders produce similar antibodies (anti-ganglioside antibodies) in cerebrospinal fluid (CSF).

MFS usually develops slowly over time, which can help doctors distinguish it from brainstem strokes that happen suddenly. Special imaging tests (like CT, MRI or MRA) and electrical tests of nerve function (like EMG, nerve conduction or evoked potential studies), among others, can help rule out these other diagnoses.

If a patient is suspected to have a serious case of either a GBS variant or brainstem encephalitis, the treatment plan doesn’t change – they would still receive Intravenous Immunoglobulin (IVIG) or a plasma exchange.

What to expect with Miller Fisher Syndrome

People with Miller Fisher Syndrome (MFS) usually have a positive outcome, with less than 5% passing away from this condition. The typical recovery time is around 8 to 12 weeks. However, some people might experience lingering symptoms, and there have been reports of the condition recurring.

In contrast, Guillain-Barre Syndrome (GBS) has a different set of challenges. In GBS, having low sodium levels in the blood (known as hyponatremia) is a sign that someone may have a more severe experience with GBS. This can be due to a condition known as syndrome of inappropriate antidiuretic hormone secretion (SIADH), where the body produces too much of a hormone that prevents urine production, leading to water retention and low sodium levels in the blood.

About 21 to 48% of people with GBS might experience hyponatremia. Earlier studies showed that hyponatremia was a strong sign of possible severe outcomes in people with GBS, but more recent research has challenged this. The latest studies suggest that how well someone is breathing, and if they experience additional medical issues while in the Intensive Care Unit (ICU), are the most reliable factors for indicating the potential severity of GBS.

Possible Complications When Diagnosed with Miller Fisher Syndrome

The main problem most patients with GBS and MFS face is overall fatigue, as noted by three out of four individuals. Fortunately, patients with MFS tend to recover better. About a third of all patients still feel pain even one year after symptoms first appear. Patients who stay in the ICU for a longer time are at greater risk of serious complications such as widespread infection, pneumonia, blood clots that lead to lung blocks (often due to not moving around), and stomach bleeding. Other problems can come about from patients experiencing issues with automatic functions of the body like heart rhythm disturbances, and ileus which is a disorder involving the intestines. A feared problem in ICU patients over 50 years old is the tiring of respiratory muscles, which can lead to death due to breathing failure. Among severely affected patients, 20 to 33% may not be able to walk for over 6 months after symptoms start, especially if they have a C. jejuni infection. Long-lasting pain and disability can also lead to mental health problems in patients.

Common Issues Experienced:

• Overall fatigue
• Persistent pain
• Widespread infection
• Pneumonia
• Blood clots leading to lung blocks
• Stomach bleeding
• Heart rhythm disturbances
• Ileus (intestinal disorder)
• Respiratory muscle fatigue
• Inability to walk
• Mental health problems due to chronic pain and disability

Recovery from Miller Fisher Syndrome

If a patient is released from the hospital with conditions known as Guillain-Barré syndrome (GBS) or Miller Fisher syndrome (MFS), they might need an extensive and intense program of physical therapy to regain normal function. The chances for a complete recovery depends on several factors including how severe the damage to the nervous system was, how old the patient is, complications that may arise, the patient’s motivation and the goals they set for recovery.

Before leaving the hospital, it’s vital to conduct a comprehensive assessment involving physical and occupational therapy. This helps to understand what the patient needs and determine the goals for therapy. Usually, people with GBS and MFS first start intensive therapy in acute care, often within the intensive care unit (ICU). From there, patients will move to a less intense therapy environment in the rehabilitation department or an off-site nursing/rehabilitation facility. Eventually, therapy will transition to either the patient’s home or an outpatient therapy location. This assessment looks at a variety of factors like interviews with patients and caregivers, sensory functions, inspections of the skin, range of motion in the joints, muscle strength, daily functional tasks, mobility, respiration, autonomic dysfunction (the part of our nervous system that controls things we don’t consciously direct, like heartbeat and digestion), and stamina.

The main goal of therapy is to help the patient regain as much normal muscle use as they can handle without creating pain, and to make use of supportive equipment to help them return to as close to their normal activities as possible. These activities must be increased slowly, with lots of muscle repetitions at low resistance to avoid injury. It will also be important to teach the patient how to conserve energy and train caregivers how to help the patient move about at home. Overall, physical and occupational therapy are crucial for recovery and management of GBS and MFS. A good plan of care can help the patient minimize pain, increase strength and stamina, and prevent issues like overuse of muscles and joints. This plan can also improve balance and mobility, as well as restore a patient’s ability to perform everyday functions.

Preventing Miller Fisher Syndrome

What is Miller Fisher Syndrome and Guillain-Barre Syndrome?

Miller Fisher Syndrome (MFS) and Guillain-Barré syndrome (GBS) are rare neurological conditions which can cause various degrees of muscle weakness. They can result from pronounced reactions of the immune system against proteins found in our nerves which are essential for movement and sensation. These reactions often occur after certain bacterial or viral infections, attacking the nerves instead of the source of the infection. This, unfortunately, can damage the nerves leading to the symptoms. Such infections often come from foods or environmental sources, with the most common triggers being the Campylobacter jejuni bacterium, which causes stomach discomfort and diarrhea, and viruses such as HIV, Epstein-Barr (which causes mononucleosis), and Zika virus.

What are the symptoms of Miller Fisher Syndrome?

Individuals suffering from MFS often experience weakness in their muscles and eyes equally on both sides of their body. This can result in difficulty walking and maintaining balance. The syndrome may start in the legs and progressively spread to the arms and face. In severe cases, muscle movement can be lost in these areas, and it can even affect the muscles used for breathing. Other symptoms can include:

1. Tingling or lack of sensation in hands or feet
2. Pain in the back, legs, or arms
3. Problems with eye movement and/or blurred vision
4. Loss of coordination in arms and legs

What tests are used to diagnose Miller Fisher Syndrome?

The doctor will typically ask about symptoms and carry out a physical examination. Additionally, they will conduct a few tests to confirm the diagnosis:

1. Lumbar puncture (spinal tap): The doctor inserts a thin needle into the lower back to draw some spinal fluid, which surrounds the brain and spinal cord, for further testing.
2. Antibody testing: The doctor may take a blood sample to see if there are certain immune components present that indicate MFS.
3. Nerve conduction studies: These tests show whether the nerves are conducting electrical signals correctly.
4. Electromyography (EMG): This test checks if muscles are responding appropriately to electrical signals from the nerves.

Scans like CT or MRI of the spine could be taken to check whether the body is attacking nerve cells in the spinal cord.

How is Miller Fisher Syndrome treated?

Miller Fisher Syndrome is treated similarly to GBS which involves varying methods based on the severity of the condition.

1. Initial treatments: Patients are typically cared for in a hospital to monitor vital signs such as heartbeat, breathing, and overall health. If breathing becomes difficult, a breathing tube may be inserted to aid the process.
2. Pain Management: Different medications might be used to manage the pain, with the proviso not to interfere with the patient’s breathing.

While there is no immediate cure for MFS and GBS, treatments like immunoglobulins (IVIG) and plasma exchange are available. IVIG aids the body in removing the harmful proteins damaging your nerves, while plasma exchange involves using a machine to remove the harmful proteins directly from the blood. Furthermore, physical rehabilitation may be required for patients with weakened muscles to regain strength and function.

How long does Miller Fisher syndrome last?

Acute MFS typically lasts for a few weeks and can be shortened with appropriate treatment. Complete recovery can take several weeks to a few months, depending on the severity of the symptoms. However, MFS usually has a milder course than other forms of GBS, so most people recover completely with no long-term muscle weakness. Only a small number of patients experience lasting muscle weakness.

How can I prevent Miller Fisher Syndrome?

As MFS and GBS can be caused by certain bacterial and viral infections, preventative measures can be taken. These include:

1. Maintaining good hygiene: Ensure you wash your hands thoroughly with soap and water before and after handling poultry or any raw meat.
2. Cooking poultry thoroughly.
3. Disinfecting water supplies.
4. Avoiding raw milk consumption.
5. Practicing safe sex.
6. For immunocompromised patients, sticking to their medication regimen to avoid certain viral infections.