Miller Fisher Syndrome
Miller Fisher syndrome (MFS) was first identified by James Collier in 1932 as a distinct triad of ophthalmoplegia (paralysis of the eye muscles), ataxia (lack of nerve-muscle coordination involuntary movements such as walking or picking up objects, which is caused by damage to the brain, spinal cord, or other nerves), and areflexia (loss of reflexes). It was, however, named after Charles Miller Fisher who reported it as a limited variant of Guillain-Barré syndrome (GBS) in 1956; GBS is an umbrella term that comprises a group of post-infectious neuropathies characterized by progressive weakness and diminished or absent reflexes. It is a post-infectious disorder, the most common preceding infections being Campylobacter jejuni (C. jejuni) infection, Epstein Barr virus (EBV) infection, hemophilus influenza virus infection, and cytomegalovirus (CMV) infection, among others. The symptoms progress and reach their peak within a week (2-21 days) of onset and the diagnosis is largely determined by the characteristic clinical presentation, the medical history, cerebrospinal fluid (CSF) analysis, basic blood workup, and nerve conduction tests. The management comprises disease-modifying immunological therapies and supportive therapies aimed at alleviating the associated symptoms. Rehabilitation also plays a major role in improving the quality of life (QoL) of patients with MFS.
MFS generally begins with a weakness in the eye muscles and progresses downwards.
Common symptoms of MFS include:
Ophthalmoplegia (eye muscle weakness resulting in impaired eye movements and consequent double vision).
Ataxia (incoordination of the limbs).
Areflexia (absence of tendon reflexes).
These symptoms typically develop rapidly over a few days. Many patients develop weakness in the face, tongue, and swallowing muscles, but others also develop weakness of the limbs and breathing muscles and are then considered to have GBS-MFS overlap syndrome. After an infection, MFS can occur for several days or up to four weeks later.
The diagnosis of MFS is made based on the clinical presentation, electromyography (EMG) and nerve conduction studies, and cytopathology (manifestations of disease at the cellular level). Nerve conduction studies and EMG are not only useful in diagnosing GBS but also in establishing the subtype. A lumbar puncture is indicated in every suspected case of GBS. Albuminocytologic dissociation in CSF is seen in 9 out of 10 patients with GBS, within 1 week of the onset of symptoms. The definite diagnostic criteria for GBS, which also apply to its MFS-variant, are summarized below:
Clinical presentation of progressive weakness in >1 limb, and areflexia.
CSF findings of albuminocytologic dissociation.
Typical nerve conduction tests and EMG findings.
Disease progression over days to 4 weeks, symmetry in the manifestations, mild sensory abnormalities, cranial nerve involvement, and autonomic dysfunction.
Recovery begins within 2-4 weeks.
The therapeutic regimen for MFS is nearly the same as that employed in managing GBS. It comprises immunotherapy, supportive care including pain control and respiratory support as needed, and physical and occupational rehabilitation.
Immunotherapies that elicit or intensify an immune response are termed activation immunotherapies, while those that reduce or suppress are termed suppression immunotherapies for GBS. Studies have established plasma exchange (PE) (blood plasma is a yellowish liquid component of blood that is freed from blood cells but contains proteins and other constituents of whole blood in suspension) and intravenous immunoglobulin (IVIg) as the disease-modifying treatment of GBS. Treatment with plasma exchange (PE) or intravenous immunoglobulin (IVIg) hastens recovery from GBS. PE and IVIg are equally effective in patients with advanced GBS symptoms. PE may carry a greater risk of side effects and is more difficult to administer. The complications of PE comprise hypotension (lower than normal blood pressure), septicemia (infection in the blood), hypocalcemia (lower than normal calcium levels in the blood), and abnormal clotting. The absolute contraindications to IVIg treatment include selective IgA deficiency, and anaphylaxis (life-threatening, severe allergic response to a drug) from previous Ig infusion, while the relative contraindications comprise cardiac (heart) and renal (kidney) failure. The common adverse effects of IVIg include malaise, fever, chills, headache, nausea, vomiting, and rashes.