What are the typical clinical presentation, diagnostic work‑up (including anti‑GQ1b antibody testing and nerve conduction studies), and first‑line treatment (intravenous immunoglobulin dosing or plasma exchange) for Miller Fisher syndrome?

Miller Fisher Syndrome: Clinical Presentation, Diagnosis, and Treatment

Clinical Presentation

Miller Fisher syndrome (MFS) is diagnosed by the classical triad of ophthalmoplegia, ataxia, and areflexia, though incomplete forms with isolated features can occur. 1, 2

Core Features

• Ophthalmoplegia is the hallmark feature, initially presenting unilaterally before progressing to bilateral involvement in most cases 2
• Ataxia manifests as difficulty with coordination and balance, presenting as an unsteady gait 2, 3
• Areflexia (reduced or absent deep tendon reflexes) is typically present in all four extremities 2, 3
• Pupillary involvement occurs in 35-42% of MFS patients and may include anisocoria or rapidly fluctuating pupillary diameter 4, 5

Atypical Presentations

• Isolated ophthalmoplegia without ataxia or areflexia can be the sole manifestation of atypical MFS 6, 4
• Acute ataxic neuropathy (isolated ataxia) or acute ophthalmoplegia may represent incomplete forms 2
• Approximately 15% of MFS cases overlap with classical Guillain-Barré syndrome, developing limb weakness 2, 3
• MFS accounts for 5-25% of all Guillain-Barré syndrome cases 2, 3

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Diagnostic Work-Up

Immediate Actions

Obtain an immediate neurology consultation for any patient with suspected MFS to guide comprehensive evaluation and management. 1

Admit all patients to an inpatient unit capable of rapid escalation to intensive-care monitoring, as respiratory failure can develop abruptly and may be clinically silent. 1

Serologic Testing

• Perform anti-GQ1b antibody testing as the most specific confirmatory test for MFS; positivity occurs in up to 90% of cases 1, 2
• Do not delay treatment initiation while awaiting anti-GQ1b results when clinical suspicion is high, as serologic turnaround may take several days 1
• Include a broader antiganglioside antibody panel to assess for other Guillain-Barré syndrome subtypes 7, 1

Cerebrospinal Fluid Analysis

• Conduct lumbar puncture and obtain 5-10 mL of CSF to allow accurate cytological examination and protein quantification 1
• Process the collected CSF within 30 minutes of lumbar puncture to preserve cellular integrity 1
• Analyze for albumino-cytological dissociation (elevated protein with normal cell count), though protein levels may be normal in 30-50% of patients in the first week 1, 2
• Send cell count and differential, cytology for malignant cells, glucose, and viral/bacterial cultures 7

Electrophysiological Studies

• Order nerve conduction studies (NCS) and electromyography (EMG) to detect polyneuropathy and support the diagnosis 7, 1
• Look for the "sural sparing pattern" on NCS (normal sural sensory nerve action potential with abnormal median/ulnar responses), which is characteristic of GBS variants including MFS 1

Neuroimaging

• Perform spinal MRI with and without contrast to rule out compressive lesions and assess for nerve-root enhancement or thickening 7, 1
• Use brain imaging to exclude alternative diagnoses such as brain-stem stroke or demyelinating disease 1

Screening for Reversible Causes

• Screen for reversible neuropathy causes: glycated hemoglobin, vitamin B12, folate, thyroid-stimulating hormone, and vitamin B6 levels 7, 1
• Obtain complete blood count, comprehensive metabolic panel, liver enzymes, and renal function tests 1
• Measure serum creatine kinase to evaluate for concurrent myositis 1

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First-Line Treatment

Intravenous immunoglobulin (IVIG) at 0.4 g/kg/day for 5 days (total dose 2 g/kg) is the first-line treatment for Miller Fisher syndrome. 7, 1, 2

Treatment Options

• IVIG 0.4 g/kg/day for 5 days is recommended by the American Academy of Neurology as first-line therapy 1, 2
• Plasmapheresis (plasma exchange) over 5 days is an equally effective alternative to IVIG 7, 1, 2
• Note that plasmapheresis immediately after IVIG will remove immunoglobulin, so avoid sequential use 7
• Corticosteroids are not recommended as monotherapy for idiopathic MFS, but may be considered in combination with IVIG in severe cases with respiratory compromise 7, 2

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Critical Monitoring

Respiratory Function

Implement serial pulmonary function testing (vital capacity and negative inspiratory force) because 15-30% of MFS patients may require ventilatory support. 1, 2

• Apply the "20/30/40 rule": consider a patient at high risk for respiratory failure if vital capacity < 20 mL/kg, maximum inspiratory pressure < 30 cm H₂O, or maximum expiratory pressure < 40 cm H₂O 1
• Single breath count ≤19 predicts need for mechanical ventilation 1
• Measure vital capacity and negative inspiratory force serially throughout hospitalization 7, 1

Autonomic Monitoring

• Provide continuous electrocardiographic and blood-pressure monitoring to detect arrhythmias and autonomic instability 1
• Observe for signs of dysautonomia, including pupillary abnormalities and bowel/bladder dysfunction 7, 1

Neurological Assessment

• Perform daily neurological evaluations to track disease progression 7, 2
• Recognize that every severity grade of MFS warrants full diagnostic workup and early intervention because of the potential for rapid progression 1

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Prognosis

• The prognosis for MFS is generally favorable, with a case fatality rate <5% 1, 2
• Most patients recover within weeks to months, with 80% regaining independent walking ability at 6 months 1
• Recovery can continue for more than 3 years, with improvement possible even beyond 5 years after onset 7, 1
• Recurrence is rare (2-5%) 7

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Common Pitfalls

• Do not dismiss isolated ophthalmoplegia as a benign cranial neuropathy; it may represent atypical MFS requiring anti-GQ1b testing 6, 4
• Do not wait for CSF protein elevation to make the diagnosis, as it may be normal in 30-50% of patients in the first week 1, 2
• Do not overlook respiratory monitoring even in patients with mild symptoms, as 15-30% may require ventilatory support 1, 2
• Do not use corticosteroids alone for idiopathic MFS, as they are not recommended as monotherapy 7, 2