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Miller Fisher Syndrome
10 May 2005
Authors
Clinical features
In 1956, Dr. Charles Miller Fisher described three patients with the clinical triad of ophthalmoplegia, ataxia and areflexia without prominent signs of peripheral neuropathy. 1 After this publication, patients presenting with this clinical triad were referred to as having the Miller Fisher syndrome (MFS). 2,3 The initial symptom is usually diplopia and/or limb and gait ataxia. 2 The full clinical picture of ataxia, areflexia and ophthalmoplegia usually develops within 5 to 10 days. 2 The diplopia usually advances over several days and may result in a complete ophthalmoplegia (including pupil areflexia) or a pure external ophthalmoplegia (with normal pupil reflexes). Read more
Natural course and prognosis
Most patients with MFS show a monophasic and benign course of disease leading to complete remission without residual deficits. 1-3 Most patients spontaneously start to improve within 2 to 4 weeks after onset of neurological symptoms. The recovery usually is completed after weeks to months with a mean recovery time of 10 weeks. 2 However, part of the patients will develop bulbar weakness with swallowing disturbances needing intubation or progress to GBS with severe tetraparesis or respiratory insufficiency. Read more
Epidemiology
MFS is a rare disease. The incidence is not exactly known and may vary between geographic areas. Based on a survey study performed in the South-West of the Netherlands the incidence of MFS is estimated to be about 1-2 per million per year. Approximately one-third of MFS patients will progress to GBS and about 5% of GBS patients started as a MFS. Males are two times more frequently affected than females.2 MFS may affect people of all ages, including children.2
Differential diagnosis
The diagnosis is based on the clinical symptoms and the presence of serum antibodies to the ganglioside GQ1b (and GT1a). Other causes of these clinical features should be excluded. Read more
Ancillary investigations
Serum antibodies to the ganglioside GQ1b (see links) Serum in the acute stage of disease (before treatment) in more than 90% of MFS patients contains antibodies to GQ1b (and GT1a) which can be determined by ELISA. 6 Anti-GQ1b antibodies in serum from MFS patients are usually of the IgG isotype, but IgM and IgA to GQ1b may also be present. These antibodies usually disappear within weeks with clinical improvement. Antibodies to other disialosyl gangliosides, including to GT1a, GD3, GD1b and GT1ba may also be detected in lesser frequencies. Read more
Genetics
MFS does not occur in families. Polymorphisms in immune response genes may be involved in the susceptibility to develop a cross-reactive antibodies after infection leading to MFS. No genetic susceptibility genes have been identified yet, but are currently investigated.
Therapy
Supportive treatment usually is sufficient in patients with mild MFS, considering the monophasic and benign course of disease. Patients with more severe MFS, developing swallowing disturbances or progression to GBS, may benefit from specific treatment although no randomised controlled trials have been performed to demonstrate treatment efficacy. Based on the parallels with GBS and on the results of case studies in MFS patients, treatment with intravenous immunoglobulin or plasma exchange may be effective in these patients. The effect of the combination of intravenous immunoglobulin and methylprednisolone is unknown. Treatment with methylprednisolone alone has not been studied in MFS, but the results in GBS indicate that it is not effective.
References
Miller Fisher. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 1956;255:57-65. Read more
Miller Fisher syndrome (MFS) is a post-infectious, immune mediated neuropathy characterized in typical cases by the clinical triad of ophthalmoplegia, ataxia and areflexia. MFS is considered to be a variant of the Guillain-Barré syndrome (GBS). The clinical symptoms usually develop within days and improve spontaneously or after treatment within weeks. Patients frequently show only part of the clinical triad. Some patients may have involvement of other cranial nerves (including facial and lower bulbar nerve) and paresis of neck, shoulder and arm musculature or may progress to GBS. Although MFS is primarily a clinical syndrome, the detection of anti-ganglioside antibodies in serum, CSF studies for increased protein content, EMG, and brainstem MRI can be helpful in making the diagnosis. More than 90% of MFS patients have serum antibodies to the gangliosides GQ1b and GT1a, but these may also be found in patients with (rare) overlapping syndromes. These antibodies are most likely induced during antecedent infection by molecular mimicry and are pathogenic for peripheral nerves in animal bioassays. MFS patients with severe MFS, bulbar weakness or progression to GBS may benefit from treatment with intravenous immunoglobulin or plasma exchange, although the therapeutic effects have not been studied in randomised controlled studies.
Authors
B.A. Jacobs, M.D., Ph.D.
P.A. van Doorn, M.D., Ph.D.
Clinical features
In 1956, Dr. Charles Miller Fisher described three patients with the clinical triad of ophthalmoplegia, ataxia and areflexia without prominent signs of peripheral neuropathy. 1 After this publication, patients presenting with this clinical triad were referred to as having the Miller Fisher syndrome (MFS). 2,3 The initial symptom is usually diplopia and/or limb and gait ataxia. 2 The full clinical picture of ataxia, areflexia and ophthalmoplegia usually develops within 5 to 10 days. 2 The diplopia usually advances over several days and may result in a complete ophthalmoplegia (including pupil areflexia) or a pure external ophthalmoplegia (with normal pupil reflexes). Read more
Natural course and prognosis
Most patients with MFS show a monophasic and benign course of disease leading to complete remission without residual deficits. 1-3 Most patients spontaneously start to improve within 2 to 4 weeks after onset of neurological symptoms. The recovery usually is completed after weeks to months with a mean recovery time of 10 weeks. 2 However, part of the patients will develop bulbar weakness with swallowing disturbances needing intubation or progress to GBS with severe tetraparesis or respiratory insufficiency. Read more
Epidemiology
MFS is a rare disease. The incidence is not exactly known and may vary between geographic areas. Based on a survey study performed in the South-West of the Netherlands the incidence of MFS is estimated to be about 1-2 per million per year. Approximately one-third of MFS patients will progress to GBS and about 5% of GBS patients started as a MFS. Males are two times more frequently affected than females.2 MFS may affect people of all ages, including children.2
Differential diagnosis
The diagnosis is based on the clinical symptoms and the presence of serum antibodies to the ganglioside GQ1b (and GT1a). Other causes of these clinical features should be excluded. Read more
Ancillary investigations
Serum antibodies to the ganglioside GQ1b (see links) Serum in the acute stage of disease (before treatment) in more than 90% of MFS patients contains antibodies to GQ1b (and GT1a) which can be determined by ELISA. 6 Anti-GQ1b antibodies in serum from MFS patients are usually of the IgG isotype, but IgM and IgA to GQ1b may also be present. These antibodies usually disappear within weeks with clinical improvement. Antibodies to other disialosyl gangliosides, including to GT1a, GD3, GD1b and GT1ba may also be detected in lesser frequencies. Read more
Genetics
MFS does not occur in families. Polymorphisms in immune response genes may be involved in the susceptibility to develop a cross-reactive antibodies after infection leading to MFS. No genetic susceptibility genes have been identified yet, but are currently investigated.
Therapy
Supportive treatment usually is sufficient in patients with mild MFS, considering the monophasic and benign course of disease. Patients with more severe MFS, developing swallowing disturbances or progression to GBS, may benefit from specific treatment although no randomised controlled trials have been performed to demonstrate treatment efficacy. Based on the parallels with GBS and on the results of case studies in MFS patients, treatment with intravenous immunoglobulin or plasma exchange may be effective in these patients. The effect of the combination of intravenous immunoglobulin and methylprednisolone is unknown. Treatment with methylprednisolone alone has not been studied in MFS, but the results in GBS indicate that it is not effective.
References
Miller Fisher. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 1956;255:57-65. Read more
DNA Diagnostics
Ganglioside-antibodies
