What are the diagnostic criteria and differential diagnoses for Miller Fisher syndrome?

Diagnosis of Miller Fisher Syndrome

Miller Fisher syndrome (MFS) is diagnosed based on the clinical triad of ophthalmoplegia, ataxia, and areflexia, with confirmation by anti-GQ1b antibody testing, which is positive in up to 90% of cases and represents the most specific confirmatory test available. 1, 2, 3

Clinical Diagnostic Criteria

The Classic Triad (Present in Most Cases)

• Ophthalmoplegia: Eye movement abnormalities are the hallmark feature, though may initially present unilaterally before progressing to bilateral involvement 2, 3
• Ataxia: Difficulty with coordination and balance, manifesting as unsteady gait 1, 4, 2
• Areflexia: Reduced or absent deep tendon reflexes, typically in all four extremities 1, 4, 3

Incomplete Forms

Recognize that MFS can present without the complete triad—isolated ataxia (acute ataxic neuropathy) or isolated ophthalmoplegia (acute ophthalmoplegia) occur in a subset of patients. 1, 2, 5 Approximately 29-30% of MFS patients exhibit atypical manifestations beyond the classic triad, including headache, delayed facial palsy, divergence insufficiency, and taste impairment. 6

Laboratory Confirmation

Anti-GQ1b Antibody Testing (Most Important)

• Anti-GQ1b antibodies are found in up to 90% of MFS patients and have the greatest diagnostic value—order this test in all suspected cases. 1, 3
• A positive result provides strong diagnostic confirmation, especially when clinical features are incomplete 1
• A negative result does not rule out MFS, but should prompt consideration of alternative diagnoses 1
• Do not delay treatment while awaiting antibody results 1

Cerebrospinal Fluid Examination

• Perform lumbar puncture to rule out alternative diagnoses and look for albumino-cytological dissociation (elevated protein with normal cell count). 1, 3
• Protein levels are normal in 30-50% of patients in the first week and 10-30% in the second week, so normal CSF protein does not exclude MFS 1, 3
• Marked pleocytosis (>50 cells/μl) suggests alternative pathologies such as infectious or inflammatory disease 1

Additional Laboratory Testing

• Complete blood counts, glucose, electrolytes, kidney and liver function to exclude metabolic causes of acute flaccid paralysis 1
• Testing for preceding infections (particularly Campylobacter jejuni) provides epidemiological information but does not confirm diagnosis 1, 7

Differential Diagnoses

Neurological Conditions to Exclude

• Bickerstaff brainstem encephalitis: Similar triad of ophthalmoplegia, ataxia, and areflexia, but distinguished by pyramidal tract signs and impaired consciousness 1
• Classic Guillain-Barré syndrome: MFS overlaps with classical sensorimotor GBS in approximately 15% of patients, presenting with additional limb weakness 1, 4, 2
• Myasthenia gravis: Consider when ophthalmoplegia is prominent, but typically lacks ataxia and areflexia 8
• Botulism: Presents with descending paralysis and ophthalmoplegia but with preserved reflexes initially 8

Brainstem and Cerebellar Pathology

• Acute cerebellitis: Presents with truncal ataxia and dysmetria, but may have altered consciousness, increased intracranial pressure, or hydrocephalus 1
• Brainstem stroke: Acute onset with focal brainstem signs; imaging reveals infarction 1
• Multiple sclerosis/demyelinating disease: Can cause ataxia and ophthalmoplegia but typically has relapsing-remitting course 1
• Posterior fossa mass lesion: Primary or metastatic tumors can present with ataxia; imaging is diagnostic 1

Toxic and Metabolic Causes

• Wernicke encephalopathy: Ophthalmoplegia, ataxia, and confusion in setting of thiamine deficiency; reflexes typically preserved 1
• Metronidazole toxicity: Shows increased T2 signal in dentate nuclei on MRI 1
• Chronic ethanol abuse: Can cause cerebellar atrophy and ataxia 1

Infectious Etiologies

• Leptomeningeal infection or malignancy: Excluded by CSF examination showing marked pleocytosis 1
• Bacterial meningitis: Fever, meningismus, and CSF pleocytosis distinguish this from MFS 1

Critical Pitfalls to Avoid

• Do not wait for anti-GQ1b antibody results before initiating treatment if clinical suspicion is high. 1
• Do not dismiss MFS diagnosis based on normal CSF protein in the first week of illness. 1, 3
• Do not overlook incomplete forms—isolated ophthalmoplegia or ataxia without the full triad can still represent MFS. 1, 5
• Monitor respiratory function closely with serial vital capacity and negative inspiratory force measurements, as 15-30% of cases require ventilatory support. 2, 3