What is Miller Fisher Syndrome
Miller Fisher syndrome (MFS) is a rare autoimmune variant of Guillain-Barré syndrome characterized by the classic clinical triad of ophthalmoplegia (eye movement abnormalities), ataxia (difficulty with coordination and balance), and areflexia (reduced or absent deep tendon reflexes). 1, 2
Core Clinical Features
The diagnosis of MFS is based on recognizing the three cardinal manifestations that define this condition 2:
- Ophthalmoplegia: Paralysis or weakness of the extraocular muscles causing double vision and inability to move the eyes normally, which is the most distinctive feature separating MFS from other GBS variants 1, 2
- Ataxia: Unsteady gait and difficulty with coordination and balance, often presenting early in the disease course 1, 2
- Areflexia: Diminished or absent deep tendon reflexes throughout the body, typically beginning in the lower limbs 1, 2
Epidemiology and Variants
MFS accounts for approximately 5-25% of all Guillain-Barré syndrome cases, making it a relatively uncommon presentation 1, 2. The condition demonstrates overlap with classical sensorimotor GBS in approximately 15% of patients, who may develop ascending weakness in addition to the classic triad 1, 2.
Incomplete forms of MFS can occur, presenting diagnostic challenges 2:
- Isolated acute ataxic neuropathy (ataxia without ophthalmoplegia) 2
- Acute ophthalmoplegia alone (eye movement problems without ataxia) 2
Pathophysiology and Triggers
Like other GBS variants, MFS is an immune-mediated polyradiculoneuropathy that typically follows an infectious trigger 3. The condition is strongly associated with anti-GQ1b antibodies, which are present in more than 90% of affected patients and serve as a sensitive and specific diagnostic marker 4, 5. Recent viral or bacterial infection within the preceding 6 weeks is common, with documented triggers including Campylobacter jejuni, Epstein-Barr virus, and other pathogens 5, 6.
Diagnostic Confirmation
The American Academy of Neurology recommends diagnosing MFS based on the classical triad with confirmation through anti-GQ1b antibody testing and supportive cerebrospinal fluid findings 2. Key diagnostic features include:
- Positive anti-GQ1b antibodies (present in >90% of cases) 4, 5
- Cerebrospinal fluid showing albuminocytological dissociation (elevated protein with normal cell count), though this may be absent early in the disease course 7, 6
- Electrodiagnostic studies may show findings consistent with demyelinating or axonal neuropathy 2
Clinical Course and Prognosis
The prognosis for MFS is generally favorable, with a case fatality rate of less than 5% and most patients recovering within weeks to months 2. Recovery can be expected in approximately 90% of cases, though full neurological recovery may take up to 2 years in some patients 8. Ophthalmologic recovery typically precedes peripheral neurologic recovery by 6 months to 1 year 9.
Treatment Approach
Intravenous immunoglobulin (IVIG) at 0.4 g/kg/day for 5 days (total dose 2 g/kg) is the first-line treatment for MFS 1, 2. Plasmapheresis over 5 days represents an equally effective alternative 1, 2. Corticosteroids are not recommended as monotherapy but may be considered in combination with IVIG in severe cases with respiratory compromise 1.
Critical Monitoring Requirements
Despite the generally favorable prognosis, 15-30% of MFS cases may require ventilatory support due to respiratory muscle involvement 1, 2. Essential monitoring includes: