Introduction

What is miller fisher syndrome?

Miller Fisher syndrome (MFS) is described as a rare variant of a neurological disorder known as Guillan-Barré syndrome (GBS). MFS is thought to occur following an acute infection. Examples of these include campylobacteriosis or mononucleosis, which are caused by the bacteria campylobacter jejuni and the Epstein-Barr virus, respectively.¹ Upper respiratory tract infections and gastroenteritis are also causative agents.²

It is therefore considered to be an autoimmune disease because an aberrant immune response to this infection causes healthy cells to become targeted as foreign. If you have MFS, you are likely to have antibodies against a molecule called ganglioside GQ1b. These are known as autoantibodies and can lead to nerve damage and the unpleasant symptoms associated with MFS.³

Guillan-barré syndrome

As mentioned previously, GBS is a more common neurological disorder, of which MFS is a subtype. Like MFS, an infectious disease typically precedes the onset of GBS, and it is the autoimmune response that causes damage to nerves and symptoms to present, including progressive muscle weakness and a decreased or absent reflex response. Numbness, pain, and dysautonomia are also common.⁴ The latter refers to a problem with the normal functioning of the autonomic nervous system, the purpose of which is to regulate processes in the body that we don’t control or think about, for instance, digestion and blood pressure.⁵

Understanding miller fisher syndrome

Symptoms of miller fisher syndrome

MFS typically presents as a triad of ophthalmoplegia, ataxia, and areflexia.

Ophthalmoplegia, or paralysis of the eye muscles, usually affects both eyes and can be internal and external. Internal ophthalmoplegia affects the muscles that control eye movement, whereas the external form causes problems with pupil constriction and lens adjustment.

Ataxia refers to problems with walking and balance, as well as functions like speaking and swallowing. It can often be severe in patients with MFS.

Areflexia is the medical term for the absence or lack of reflexes in the body, attributable to the nerve damage caused by a prior infection.

Other associated symptoms include double or blurred vision, drooping of the eyelids, and features of dysautonomia, for instance, dizziness and low blood pressure.^1,2,3

Diagnosis of miller fisher syndrome

To diagnose MFS, a lumbar puncture can be performed. During this procedure, a needle is inserted into your lower back to withdraw a sample of cerebrospinal fluid. This is found in the space surrounding the spinal cord and brain and serves to protect these areas. The presence of anti-GQ1b antibodies in cerebrospinal fluid can confirm the presence of MFS.

Furthermore, nerve conduction studies that show reduced or absent sensory responses may indicate a diagnosis of MFS. Imaging tests, including computed tomography (CT) and magnetic resonance imaging (MRI), can also be useful for identifying changes in the brain and spinal cord structure associated with this disorder.^1,3

The Brighton criteria state the features that a patient with suspected MFS should be presenting with in order for a diagnosis to be confirmed.⁶

Treatment of miller fisher syndrome

You will usually stay in the hospital for several weeks for the immediate treatment of MFS, albeit rehabilitation to treat the long-term effects of the condition can continue for months or even years after you first develop MFS.  

Intravenous immunoglobulin therapy

Similar to GBS, intravenous immunoglobulin (IVIg) therapy is the recommended treatment for MFS. It consists of administering antibodies from the donated blood of a healthy individual to help stop the nerve damage caused by harmful antibodies that are produced by your immune system. During this treatment, antibodies are given directly into a vein.

IVIg therapy should be given as soon as possible to reduce the possibility of sustaining irreversible, long-term neuronal damage, and also to provide the best possible prognosis for your condition.⁷

Plasma exchange

This is also known as plasmapheresis and helps to regulate your immune system. During the procedure, you are attached to a machine that removes and filters the harmful antibodies out of your blood, before it is delivered back into your body.⁷  

IVIg therapy and plasma exchange - is there a preference?

Both treatment methods are thought to be equally effective.⁸ Plasma exchange is considerably cheaper than IVIg therapy, but specific equipment is required, and the procedure carries risks such as the formation of blood clots as well as infection at the site at which the machine is connected to a vein in your body. Allergic reactions can occur, too. IVIg therapy is more expensive, but the likelihood of adverse effects is decreased, which arguably makes it the preferred treatment option.^1,7

Corticosteroids

The use of corticosteroids for MFS treatment has mostly been discredited owing to their inability to aid recovery and optimise prognosis. When combined with IVIg therapy, little improvement is noted, albeit when used in the early stages of MFS, this combination treatment may provide some benefit.^7,9

Supportive treatments

Symptomatic management

In addition to the above treatments, there are methods that can be used to relieve any additional symptoms you may be experiencing:

• Painkillers – mild analgesics (i.e. paracetamol) can alleviate pain, or drugs like morphine and oxycodone can be used for more severe pain
• Ventilator – this is a machine that helps you to breathe more easily
• Feeding tube – medically known as a nasogastric tube, this provides you with nutrition if you have swallowing problems
• Bladder catheterisation – this is a tube that can relieve urinary retention
• Laxatives – these are a class of medications that treat constipation
• Compression stockings – these reduce the risk of blood clots, which are common during prolonged periods of rest in hospital¹

Rehabilitation

Upon being discharged from the hospital, a comprehensive physical therapy programme should be designed to enable optimal recovery from your condition. Goals should be set that will allow you to resume functional activity as close as possible to your pre-illness level, whilst also factoring in pain management.

Energy conservation, or pacing, helps you to establish a balance of rest and activity to avoid a ‘crash’. These describe periods of time in which your symptoms have worsened.¹

Emerging treatments

Neonatal Fc receptor

The role of the neonatal Fc receptor (FcRn) is to transfer antibodies from the mother to the offspring during pregnancy.¹⁰ Inhibiting this receptor has been shown to reduce antibody levels in mice, thus reducing nerve damage and its associated symptoms. This research suggests that FcRn inhibitors may be an alternative treatment option for MFS in the future.¹¹

Eculizumab

The anti-GQ1b antibodies which are present in MFS, destroy the neuromuscular junction, which is the space between nerves where electrical impulses are transmitted. This damage leads to the accumulation of a complex known as C5b-9 in nerves.⁷ 

Eculizumab is an antibody that blocks the action of C5b-9, thus reducing the neurological symptoms in MFS.¹²

Dimethyl fumarate

Research has suggested that dimethyl fumarate, a disease-modifying therapy, can improve demyelination in rats with a condition that similarly resembles MNF. Demyelination is used to describe damage to the myelin sheath, a protective covering that surrounds nerve cells, and is representative of the neurological changes that occur in MNF.¹³ 

Prognosis and long-term outcomes

MFS is rarely fatal, although prognosis is dependent on you as an individual and how you respond to treatment. Most patients will recover within six months, and permanent neurological complications are uncommon. 

Summary

MFS is a rare variant of GBS, an autoimmune disorder of the nervous system that can cause symptoms such as paralysis of the eyes, ataxia and problems with your reflexes. IVIg therapy and plasma exchange are the primary treatment options for the condition, although rehabilitation and management of other symptoms are equally important too. Novel methods, such as FcRn inhibitors and eculizumab, may pave the way for future treatment of MFS, however, greater research is needed to strengthen the evidence for their efficacy.