NORD gratefully acknowledges Richard Hughes, MD, Cochrane Neuromuscular, MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery, London, UK, for assistance in the preparation of this report.
Miller Fisher syndrome (MFS) is a rare acquired nerve disease related to Guillain-Barré syndrome (GBS). Features include weakness of the eye muscles causing difficulty moving the eyes; impaired limb coordination and unsteadiness; and absent tendon reflexes. Other symptoms may include facial, swallowing and limb weakness, as well as respiratory failure. MFS can affect both children and adults. It often occurs several days (up to four weeks) after a bacterial or viral illness. MFS is rare, affecting one to two people per million each year. It is an autoimmune disease, in which the immune system attacks the nerves. Specific treatment is available but most patients recover within six months even without treatment. Very few patients have permanent neurological problems or relapse. Death is very rare.
MFS is named after Dr. Charles Miller Fisher, a Canadian neurologist working at Massachusetts General Hospital. In 1956, he described three patients with ophthalmoplegia (eye muscle weakness), ataxia (incoordination), and areflexia (absence of tendon reflexes). He deduced that their disease shared features with Guillain-Barré syndrome (GBS) to which it is related. (For more information on GBS, see https://rarediseases.org/rare-diseases/guillain-barre-syndrome/)
MFS has three defining features:
These symptoms typically develop rapidly over a few days. Some patients have weakness of the face, tongue and swallowing muscles as well. Others also develop weakness of the limbs and breathing muscles and are then considered to have GBS-MFS overlap syndrome. MFS often occurs several days or up to four weeks after an infective illness (especially Campylobacter jejuni, a diarrheal illness, or Haemophilus influenzae, a respiratory infection).
MFS is an autoimmune disease in which antibodies against a bacterial or viral infection cross-react with and attack the nerves. The site of attack may be the myelin sheaths, which insulate and protect the nerve fibers (axons), or the axons themselves. The principal autoantibody is directed against a molecule called ganglioside GQ1b, which is especially present on the nerves affected. The antibody is present in the blood of at least 80% of people with MFS and can be used to confirm the diagnosis.
MFS does not usually affect more than one person in the same family. There are very rare reports of siblings or identical twins being affected. It is thus possible that there is a hereditary predisposition to develop the disease. It is not infectious.
MFS is rare, affecting only one to two people per million each year in most parts of the world. It is more common in East Asia. It affects both children and adults. It is more common in men than women and in the young than the old. The average age of onset is 45 years.
MFS is often hard to diagnose because it can mimic other neurologic diseases such as myasthenia gravis, botulism, diphtheria, brain stem stroke, brain stem encephalitis and basal meningitis. Physicians should have a high index of suspension, rule out similar diseases and consider testing for anti-GQ1b antibody to help diagnose Miller Fisher syndrome.
Clinical Testing and Work-Up
The diagnosis of MFS is clinical. It depends on identifying the characteristic features from the symptoms and physical examination. There is no definitive diagnostic test. Antibodies against ganglioside GQ1b support the diagnosis but also occur in Bickerstaff brainstem encephalitis. As in GBS, the cerebrospinal fluid often shows a high protein while the cell count remains normal. The sample of cerebrospinal fluid is collected by a spinal tap (lumbar puncture). In a third of patients with Bickerstaff brainstem encephalitis the cell count is increased.
Nerve conduction tests (electromyography) are often done to support the diagnosis. In MFS, the tests on the motor nerves are usually normal but the sensory nerve action potentials are absent and there are abnormalities of the sensory nerves which produce the tendon reflexes. The tests involve recording of the muscle or sensory nerve fiber activity following small electric shocks to the nerves.
Magnetic resonance imaging (MRI) of the brain may be done as part of the diagnostic work up. It is usually normal in MFS but may show abnormalities in the brain stem in Bickerstaff brainstem encephalitis. In GBS, it usually shows enhancement (increased signal) in the spinal nerve roots following injection of a radio-opaque dye.
Most patients recover within six months. The average recovery time is 8 to 12 weeks. The disease rarely causes permanent neurological problems. Relapse occurs in less than 3 percent of patients. Death is very rare. Supportive care to manage the physical and emotional challenges of the disease is needed. Good nursing, physical therapy, occupational therapy and psychological support are important.
Because the prognosis is so good and clinical trials have not been done, it is not known whether specific treatment helps. However, because MFS is related to GBS and may progress to MFS-GBS overlap syndrome, the usual treatments for GBS are often given. These are intravenous immunoglobulin (IVIg) or plasmapheresis (plasma exchange). Steroids are not used since they are not beneficial in GBS. The initial treatment is usually IVIg. IVIg consists of infusions of high doses of immune globulin (the antibodies in the blood) into a vein. It is usually given daily for five days. The immune globulin comes from highly purified, pooled plasma from thousands of healthy people. It is believed to work by blocking the effects of the antibody that causes the disease. Plasmapheresis is a procedure that removes antibodies from the blood. One vein is connected via a thin plastic tube to a machine which separates the plasma (the liquid portion of the blood) from the red blood cells and returns the red blood cells with a plasma substitute into another vein. It is usually done five times over about two weeks. IVIg is more convenient and widely available than plasmapheresis.
An international observational study enrolling more than 2,000 patients https://gbsstudies.erasmusmc.nl/ aims to identify clinical and biological determinants and predictors of Guillain-Barré syndrome and overlap syndromes, including MFS. This information will be used to understand the disease and treatment response.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
However, there are currently no investigational therapies for MFS listed on this or other similar sites.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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