Complications And Long-Term Outcomes Of Miller Fisher Syndrome

In 1956, Miller Fisher Syndrome was “[classified] as a unique entity within the GBS spectrum” by the very man after whom the disease is named (the Canadian neurologist, Miller Fisher).¹ Since then, there have been conflicting “interpretations of the nature of the Miller-Fisher syndrome”.²

However, when reading up on Miller Fisher Syndrome (MFS), one is most likely to find sources quoting MFS as being one of the four 4 main subtypes of Guillain-Barré Syndrome (GBS).^1,2,3 

Since MFS is such an incredibly rare subtype of GBS, having “a worldwide prevalence of 1 in 1,000,000”^1,4,5 compared to the 1 to 2 people per 100,000^1,4,6,7 for all/any GBS subtype(s), data on MFS is relatively hard to come by. For instance, a MFS literature review conducted in 1992 stated that only 223 cases of MFS had been published in the 36 years following a report in 1956.² This sparsity of data, therefore, is why this article may refer, in some instances, to statistics/data non-specific to any one subtype of GBS rather than just MFS.

Of course, this article’s sole aim is to investigate the long-term outcomes and complications of only the MFS subtype; any statistics non-specific to MFS, used in this article, are only intended to help the reader gauge an approximation of whatever matter it is that is being discussed.

Understanding miller-fisher syndrome 

MFS is a rare neurodegenerative autoimmune condition, usually only ever responsible for one episode of symptoms (monophasic/non-relapsing) and normally occurring after a recent infection.

The words ‘autoimmune’ and ‘immune-mediation’ are often used to describe MFS. These words convey that MFS is a disease where your own body is responsible for the damage that is done (in this case, to the nervous system). 

In MFS, the most established and thoroughly studied mechanisms with which the body does damage to nerves are ‘antibody-mediated’ (meaning a mechanism whereby damage is done ‘via antibodies’); antibodies are a class of weapon made by your immune system in order to fight any one specific species of germ. However, autoimmune diseases can begin when antibodies end up accidentally targeting certain structures in your own cells (i.e. different structures on your nerves in MFS).

To be specific, in MFS these antibodies are believed to damage nerves by causing their demyelination.⁸ Demyelination is when damage is done to a structure surrounding our nerves called the ‘myelin sheath’. 

In simple terms, the myelin sheath serves an analogous role to that of plastic insulation around copper wires (in this analogy, it is the copper wire which represents the nerve). Damage to the myelin sheath, therefore, results in the reduced conductivity of electrical signals through the nerve.

There are two main nerve types in which demyelination caused by the MFS subtype can affect:

• Motor neurones: nerves that carry messages/orders out from the brain and spinal cord to muscles. Damage to motor neurones gives rise to symptoms such as weakness and paralysis
• Sensory neurones; these send signals received from skin and muscles (such as pain) back to the brain and spinal cord. When damaged, symptoms such as numbness may arise

These two main nerve types exist outside of the Central Nervous System (CNS; this is the brain and spinal cord) and are also affected in other GBS subtypes. In MFS, however, there is also involvement of other aspects of the nervous system, with there being “evidence for involvement of brainstem structures in the Miller Fisher syndrome.”² Likewise, EEG, MRI and CT scan findings have been “reported as evidence for a central nervous system involvement”^2,9 in MFS. 

Again, unlike other GBS subtypes, MFS does not “ever show the involvement of the autonomic system”² (the autonomic system comprises nerves associated with internal organs).

Symptoms

The main triad of symptoms which indicate MFS are:⁴

• Ataxia: loss of coordination and balance
• Areflexia; absent tendon reflexes
• Ophthalmoparesis: weakness or paralysis of the eye muscle(s) leading to trouble with eye movement

Other common MFS symptoms include:

• Difficulty breathing
• Difficulty swallowing 
• Double vision
• Difficulty moving facial muscles; this can also lead to dysarthria(difficulty with articulation) 
• Tingling and numbness (especially in the face)

Causes and risk factors

There are several associated microorganisms associated with MFS, most notably Campylobacter jejuni,¹⁰  Zika virus,¹¹ “human immunodeficiency virus (HIV), as well as Haemophilus influenzae.”1,4,6 Furthermore, MFS has also been associated with SARS-CoV-2 (COVID-19) infection.^1,6 Other analyses showed evidence that patients suffering GBS subtypes had previously been infected with Mycoplasma pneumoniae, hepatitis E virus, cytomegalovirus, and Epstein-Barr virus.^12,13

Having said this, MFS patients do not always report having had a recent infection; one source demonstrated that in 12.6% of MFS cases, “no preceding illness was mentioned”² Such incidents, where no prior infection is reported, may be explained by “exposure to toxins [or] genetics”¹ with documented incidents of GBS even affecting multiple family members. ^14,15

Various sources show a range of “other risk factors associated with [MFS]”:^4,7,16

“Other risk factors associated with [MFS] include the use of certain drugs (heroin, suramin, streptokinase, and isotretinoin), use of TNF-alpha antagonist therapy, other concurrent autoimmune diseases (systemic lupus, Hodgkin disease, and sarcoidosis), surgery, epidural anaesthesia, bone marrow transplant, and immunizations.”

Age and sex are also risk factors, with MFS having a male to female ratio of 2:1 and a mean onset age of 43.6 years old.²

Another report found that in all subtypes of  “GBS incidence increased by 20% for every 10-year increase in age”.¹⁷

Furthermore, MFS incidence is higher in Asian countries where it accounts for “15-20% of GBS cases”^1,6 whereas it only “makes up about 5% of the cases of GBS in most[/other] countries”.^4,17,18

Long-term outcomes and prognosis 

Though there are limited studies reviewing the long-term outcomes of large numbers of MFS cases, individual case reports often show “remarkable recovery”¹⁹ and “improvement in functional outcomes”^20,21 following post-treatment rehabilitation and physiotherapy.

In all GBS subtypes, there are usually four key consecutive phases which often succeed in describing the changes to the severity of the disease in patients:²²

• Progression: This immediately happens with the onset of GBS and means that symptoms get progressively worse, usually at a fast rate
• Plateau: a period when no (or very limited) change in the disease severity is observed. This can last from a few days to a few weeks or even months. This phase can result in patients struggling with symptoms such as muscle weakness and/or balance problems for a substantial period after treatment
• Recovery; gradually, certain symptoms begin to subside over a period of months and years. The extent and speed of recovery may be affected by various factors such as age, diet, genetics and engagement with physiotherapy 
• Disability; most patients recover to an extent that they can function normally in day-to-day life, however, some residual symptoms may linger for large portions, if not the rest, of their lives

There is, generally, strong consensus as to the nature of the initial progression phase. One paper stated that GBS reaches its “maximal severity within 4 weeks”;²³ another described a study showing “that 80% of patients with GBS reach the [maximum severity of their symptoms] within 2 weeks after onset of weakness, and 97% reach the [maximum severity of their symptoms] within 4 weeks.”²⁴ 

The plateau is also variable, “ranging from 2 days to 6 months”;²⁴ however, “most patients start recovering within less than a week”²⁶ of having reached the maximum severity of their symptoms. 

“Although most people have an uneventful recovery, 15 to 20% of GBS patients are left with severe neurologic deficits.”²⁵ “In mild cases, complete recovery may occur over a few weeks, although other residual effects may persist permanently.”²⁷ A few examples of residual effects include:²⁷

• Neuropathic pain
• Fatigue
• Residual muscle weakness resulting in pain from overuse
• Tremors

There have also been documented incidents of recurrent episodes of GBS^28,29 with one study finding that the mean interval between attacks was 9.45 years”²⁹ and that in “81% of the recurrent episodes, an infectious disease preceded MFS”.²⁹

Conclusion 

Miller Fisher Syndrome, a rare subtype of Guillain-Barré Syndrome, presents unique challenges due to its rarity and complex symptomatology. Understanding its autoimmune nature and associated risk factors is crucial. Despite limited data, evidence suggests that with appropriate treatment and rehabilitation, many patients experience significant recovery, highlighting the importance of early diagnosis and comprehensive care.

FAQs

Q1: What are the main symptoms of miller-fisher syndrome?

The classic triad of symptoms indicating MFS are ataxia, areflexia and ophthalmoparesis. 

Q2: Can miller-fisher syndrome be cured?

Following treatment with intravenous immunoglobulin or plasmapheresis, most patients recover, but some residual symptoms might persist.

Q3: What should I do if I experience a relapse of symptoms?

Seek immediate medical attention to manage and treat relapses.

Q4: Are there any lifestyle changes that can help manage long-term outcomes?

Maintain a healthy lifestyle and attend regular medical follow-ups.