Introduction

Miller Fisher Syndrome (MFS) is an acute neurological disorder and variant of the Guillain-Barré syndrome that is characterised by a distinctive triad of symptoms: ataxia, areflexia, and ophthalmoplegia.¹ This disease is extremely rare, affecting only one in every 1,000,000, with predominance in people assigned male at birth (AMAB) (gender ratio 2:1).²  

MFS is an autoimmune disease - the immune system is unable to recognise what is and what isn’t foreign to the body and attacks the nerves.³ The illness can affect individuals of any age, but its presentation may vary between children and adults. Understanding these differences is crucial for an effective diagnosis and management of MFS. In this article, we will explore the variations in MFS in children and adults.

Causes of miller fisher syndrome

MFS is an autoimmune disorder that typically occurs following a bacterial or viral infection. Most commonly, these are infections by the bacteria Campylobacter jejuni and Haemophilus influenzae, which cause gastrointestinal infections and respiratory infections, respectively.⁴ In both adults and children, prior respiratory infection appears to be most common.^5,6 

Following this infection, the immune system produces antibodies when trying to protect the body from the infection. In MFS patients, autoantibodies such as anti-GQ1b are also produced.⁸ Where antibodies recognise foreign cells and substances to eliminate them, autoantibodies are a ‘malfunction of the immune system’, recognising the body’s own proteins as threats. It is important to note that autoantibodies are present in all of us, with common autoantibodies helping with the body’s first line of defence against infections.⁷ 

The pathogenic autoantibodies anti-GQ1b attack the membranes of our nerves, leading to nerve damage. The nerve damage then causes the characteristic symptoms of MFS.⁹ 

The younger the child, the less developed their immune system will be. It is possible that the less mature immune systems of children may affect the development and subsequent progression of MFS. The disease may present differently in children compared to adults –  most of whom have a fully developed immune system. This is reflected in the milder presentation of the disease in children and the reduced levels of anti-GQ1b upon diagnosis. Children with MFS have also been reported to recover faster than adults with MFS.^5,10 

Symptoms of miller fisher syndrome

MFS is distinguished by three classic symptoms, present in both children and adults: 

1. Ataxia:
   • Loss of muscle coordination ¹¹
   • Abnormal walking patterns
   • Abnormal speech patterns
   • Involuntary eye movements
   • Clumsiness and difficulty controlling hand movements
2. Areflexia: 
   • Absence of tendon reflexes
   • Typical reflex reactions such as knee or ankle-jerk reflexes are either minimal or completely absent
3. Ophthalmoplegia: 
   • Paralysis or weakness of eye muscles ¹²
   • Double or blurred vision
   • Difficulty controlling eye movements
   • Drooping eyelids

However, given the damage to the nerves, other symptoms may also occur.

Here are some other signs to watch out for: ^2,13

• Headaches 
• Facial palsy: weakening of the facial muscles, may extend to the arms and legs
• Tingling, burning, ‘pins and needles’ sensation in skin
• Dizziness 
• Hypertension: high blood pressure
• Excessive sweating at night
• Increased heart rate for no reason
• Hypotonia: loss of muscle tone; muscles in arms and legs may feel soft and ‘floppy’

In children, MFS may present more subtly, with reduced simultaneous occurrence of ophthalmoplegia in both eyes, as well as increased autonomic symptoms.⁵ This refers to implications in the part of the nervous system that controls blood pressure, heart rate, respiration, and digestion.¹⁴ On the other hand, adults tend to present with symptoms more quickly and distinctly, with the reported time between the prior infection to the strong presentation of more than one of the classic symptoms being 2 weeks.¹⁵ 

Although recurrent MFS is rare, making up only a small percentage of all MFS cases, it is important to note here that it is more likely to occur in younger patients.¹⁶ Clinically, recurrent MFS presents the same as non-recurrent MFS, but the severity of the disease may vary largely. Any number of the symptoms above are a possibility upon recurrence. 

Diagnosis of miller fisher syndrome

Through the help of clinical history, physical examinations, imaging and laboratory findings, the Brighton criteria is a tool used by clinicians to aid with the diagnosis of Guillain-Barré syndrome (GBS) and its variants, including MFS.^{2, 6, 17}

This criteria includes: 

1. Bilateral and flaccid weakness of limbs
2. Absence of deep tendon reflexes in weak limbs
3. Time between onset to worst of symptoms is 12 hours to 28 days
4. Cell count in cerebrospinal fluid (CSF) is below 50 cells/microliter 
5. Protein concentration in CSF is abnormally high
6. Nerve conduction study consistent with at least one of the GBS variants 
7. Lack of alternative diagnosis for weakness

Cerebrospinal fluid (CSF) analysis

Given that elevated protein concentration without elevated white blood cell count in the CSF is a hallmark of MFS, analysing CSF contents helps to differentiate the disease from other similarly-presenting neurological conditions.²

Brain imaging 

In the brain scans of MFS patients, the brain typically presents without structural abnormalities. However, lesions have been observed in the brain stem of people with MFS, and cranial nerves, including the optic nerve, are often abnormally enhanced. This may be due to the immune response bypassing the blood-brain barrier. ^18,19 

Nerve conduction studies

Nerve conduction studies help to assess the function of the nerves, acting to reveal any nerve damage that may be present and consistent with immune-mediated attacks on the nerves.²  

Physical examination

A physical examination is crucial for the diagnosis of MFS. In a physical exam, doctors look for any sign of the classic triad of symptoms, assessing muscle strength, coordination, and control. This not only helps to diagnose the disease, but also helps with determining the severity.²

Summary 

Miller-Fisher Syndrome affects both children and adults but presents differently depending on age. Children typically have milder symptoms and faster recovery, whereas adults have more distinct and severe symptoms, accompanied by a slower recovery rate. The variation in clinical presentation, progression, and other age-respective changes in the body mean that it is important that the disease is accurately diagnosed and treatment is tailored to the patient, especially in children. Recognising the unique aspects of MFS in different age groups is vital for optimising patient outcomes and improving upon a better understanding of this illness.