Miller Fisher Syndrome

Miller Fisher syndrome is an acute, immune mediated variant of Guillain-Barré syndrome with the triad of ophthalmoplegia, ataxia and areflexia. Anti-GQ1b IgG antibodies are found in about 85 to 90% of cases, and the outcome is usually good.

It makes up about 5% of Guillain-Barré syndrome cases in Western countries and up to 20 to 25% in East Asia. The incidence is about 1 to 2 in every million people each year, with a male predominance of about 2 to 1 and a mean onset around 40 years.

Triggers. A preceding respiratory or gastrointestinal infection in 60 to 75%, most often Campylobacter jejuni or Haemophilus influenzae, 1 to 3 weeks before onset.

Overlap syndromes. Bickerstaff brainstem encephalitis (with drowsiness or hemiparesis), Guillain-Barré syndrome with ophthalmoplegia, and pharyngeal-cervical-brachial variants, all linked to anti-GQ1b antibodies.

Course. Nadir at about 2 weeks; recovery starts within 2 to 4 weeks and is complete in most within 6 months. Relapse is rare.

Pathophysiology.

Molecular mimicry between microbial lipo oligosaccharides and GQ1b ganglioside produces antibodies that bind the oculomotor nerves, muscle spindles and sensory afferents, where GQ1b is densely expressed.

Complement activation at the neuromuscular junction and nodes of Ranvier causes the clinical deficit.

• Subacute external ophthalmoplegia with diplopia, usually bilateral and symmetrical; ptosis in some; pupils fixed or dilated in a minority.
• Gait and limb ataxia with a normal strength, due to sensory ataxia rather than cerebellar disease.
• Absent or reduced tendon reflexes.
• Facial and bulbar weakness, paraesthesia, and mild limb weakness in some.

Red flags.

• Drowsiness, hemiparesis or hyperreflexia (Bickerstaff encephalitis).
• Limb weakness, bulbar failure or falling vital capacity (progression to Guillain-Barré syndrome).
• Autonomic instability (arrhythmia, blood pressure swings).

• Clinical diagnosis from the triad, supported by anti-GQ1b IgG (positive in most).
• Cerebrospinal fluid shows raised protein with a normal cell count in many, but may be normal in the first week.
• Nerve conduction studies are normal or show reduced sensory amplitudes; MRI of the brain is normal in most and excludes brainstem stroke and other lesions.
• Measure forced vital capacity and lying and standing blood pressure; exclude botulism, myasthenia gravis and Wernicke encephalopathy.
• Test for diabetes, thyroid disease and infection, including Campylobacter in stool if diarrhoea occurred.

Differential diagnosis. Brainstem stroke, Wernicke encephalopathy, myasthenia gravis, botulism, Bickerstaff encephalitis, multiple sclerosis, diphtheria, diabetic oculomotor palsies and thyroid eye disease.

• Admit for monitoring because progression to generalised weakness can occur. Many patients recover without immunotherapy, so treat severe, progressive or overlapping disease.
• Intravenous immunoglobulin: 0.4 g/kg daily for 5 days (total 2 g/kg). Maximum 2 g/kg in a course. Infusion rate is set by the product label, starting slowly. Monitor renal function, blood pressure, hypersensitivity, thrombosis, haemolysis and aseptic meningitis; check IgA before the first dose. Avoid in IgA deficiency with anti-IgA antibodies; use caution in renal impairment, heart failure and older adults; acceptable in pregnancy.
• Plasma exchange as an alternative: 5 exchanges of 200 to 250 mL/kg plasma over 1 to 2 weeks. Monitor calcium, blood pressure, coagulation and line infection. Avoid in unstable cardiovascular disease and sepsis.
• Corticosteroids and a second course of immunoglobulin are not helpful in the usual course.
• Eye care: patching or prisms for diplopia, and lubricants for exposure.
• Physiotherapy for ataxia, and falls prevention.
• Thromboprophylaxis if immobile: enoxaparin 40 mg subcutaneously once daily. Maximum 40 mg daily (20 mg daily when creatinine clearance is under 30 mL/min). Monitor platelets, renal function and bleeding. Avoid in active bleeding and heparin induced thrombocytopenia; acceptable in pregnancy.

Monitoring. Measure forced vital capacity and bulbar function daily during progression; review at 2 weeks, 3 months and 6 months.

Referral and escalation. Neurology for all patients; intensive care for falling vital capacity, bulbar failure or autonomic instability.

Special groups. Pregnancy: immunoglobulin is preferred. Older adults: risk of renal and thrombotic complications with immunoglobulin.