What are the recommended investigations for a patient with suspected Miller‑Fisher syndrome?

Miller Fisher Syndrome Investigation

The diagnostic workup for suspected Miller Fisher syndrome should include neurology consultation, anti-GQ1b antibody testing (the most specific confirmatory test), cerebrospinal fluid analysis for albumino-cytological dissociation, and electrodiagnostic studies, along with serial respiratory function monitoring given the risk of progression to respiratory failure. 1, 2

Essential Diagnostic Tests

Serology

• Anti-GQ1b antibody testing is the single most important confirmatory test, with positivity in up to 90% of MFS patients and the highest diagnostic specificity 2, 3
• This test should be ordered immediately when MFS is suspected, as it is uniquely associated with both MFS and the related Bickerstaff's brainstem encephalitis 3
• Serum antiganglioside antibody panel should also include testing for other GBS subtypes 1

Cerebrospinal Fluid Analysis

• Lumbar puncture should be performed to look for albumino-cytological dissociation (elevated protein with normal cell count), though this finding is present in only 60% of MFS cases 2, 3
• Protein levels may be normal in 30-50% of patients during the first week, so a normal CSF protein early in the disease does not exclude MFS 2
• CSF should also be analyzed for cell count and differential, cytology (to exclude malignancy in appropriate contexts), glucose, and cultures 1
• Collect 5-10 mL of CSF and process within 30 minutes to preserve cellular integrity and protein components 2

Electrodiagnostic Studies

• Nerve conduction studies and electromyography should be performed to evaluate for polyneuropathy and support the diagnosis 1, 2
• The most consistent findings in MFS are reduced sensory nerve action potentials and absent H reflexes 4
• Look for the "sural sparing pattern" (normal sural sensory nerve action potential with abnormal median/ulnar responses), which is typical for GBS variants 1
• Early testing (within 1 week) may be normal, so repeat studies in 2-3 weeks if clinical suspicion remains high 1

Neuroimaging

• MRI of spine with and without contrast to rule out compressive lesions and evaluate for nerve root enhancement or thickening 1
• Brain MRI is typically normal in MFS but may show nerve root enhancement in rare cases 4
• Neuroimaging helps exclude alternative diagnoses such as brainstem stroke or demyelinating disease 1

Critical Monitoring Parameters

Respiratory Assessment

• Serial pulmonary function testing is mandatory, as 15-30% of MFS cases may require ventilatory support 2
• Measure vital capacity and negative inspiratory force (NIF) at presentation and serially throughout hospitalization 1, 2
• Single breath count ≤19 predicts need for mechanical ventilation 2
• Apply the "20/30/40 rule": patient is at risk of respiratory failure if vital capacity <20 mL/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 1

Autonomic Function

• Continuous electrocardiographic monitoring and blood pressure surveillance to detect arrhythmias and autonomic instability 1
• Monitor for pupillary dysfunction, bowel/bladder dysfunction, and other signs of dysautonomia 1

Additional Screening Tests

• Screen for reversible neuropathy causes: HbA1c, vitamin B12, folate, TSH, vitamin B6 1
• Complete blood count, comprehensive metabolic panel, liver enzymes, and renal function to exclude metabolic causes 1
• Serum creatine kinase (CK) to evaluate for concurrent myositis, though elevation is less common in MFS than in other GBS variants 1

Consultation and Admission Criteria

• Neurology consultation should be obtained immediately for all suspected MFS cases 1, 2
• All grades warrant workup and intervention given potential for progressive disease leading to respiratory compromise 1
• Admit to inpatient unit with capability for rapid transfer to ICU-level monitoring, as respiratory failure can occur rapidly and sometimes without obvious dyspnea 1

Common Diagnostic Pitfalls

• Do not dismiss MFS based on normal CSF protein in the first week—protein elevation may develop later in the disease course 2
• Do not wait for antibody results before initiating treatment if clinical suspicion is high, as anti-GQ1b testing may take several days 1
• Isolated ophthalmoplegia without ataxia or areflexia can still represent atypical MFS, especially with positive anti-GQ1b antibodies 5
• The absence of preceding infection does not exclude MFS, though most cases follow viral or bacterial illness 6, 4