What is the appropriate management for an adult with acute Guillain‑Barré syndrome presenting with rapidly progressive symmetric limb weakness, areflexia, and potential respiratory or autonomic involvement?

Management of Guillain-Barré Syndrome

Initiate intravenous immunoglobulin (IVIg) 0.4 g/kg daily for 5 consecutive days (total 2 g/kg) immediately for any adult with acute GBS who cannot walk unaided, alongside intensive respiratory and autonomic monitoring, without waiting for confirmatory test results. 1, 2, 3

Immediate Life-Threatening Assessment

Assess respiratory function and autonomic stability at presentation as the highest priority—approximately 20% of patients develop respiratory failure requiring mechanical ventilation, which can occur rapidly and sometimes without obvious dyspnea. 1, 2

Respiratory Monitoring

• Measure vital capacity, negative inspiratory force (NIF), and maximum inspiratory/expiratory pressures at presentation and serially throughout hospitalization 1
• Apply the "20/30/40 rule": patient is at high risk of respiratory failure if vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 1, 2
• Single breath count ≤19 predicts need for mechanical ventilation 1
• Repeat pulmonary function testing daily in all patients with progressive weakness 1

Autonomic Monitoring

• Perform continuous electrocardiographic monitoring and blood pressure surveillance for arrhythmias and blood pressure instability 1, 2
• Monitor for pupillary dysfunction, bowel/bladder dysfunction, and heart rate variability 1
• Recognize that cardiovascular complications contribute to the 3-10% mortality rate even with optimal care 1, 2

Admission Criteria

Admit to an inpatient unit capable of rapid ICU transfer for Grade 3-4 disease: severe weakness limiting self-care, any dysphagia, facial weakness, respiratory muscle weakness, or rapidly progressive symptoms 1

Even Grade 2 (moderate) disease—patients with some limitation of daily activities—requires neurology consultation and close inpatient monitoring. 1

Clinical Diagnosis

The diagnosis is primarily clinical and should not delay treatment while awaiting confirmatory testing. 1, 4

Key Diagnostic Features

• Rapidly progressive bilateral ascending weakness starting in the legs and progressing to arms and cranial muscles, typically reaching maximum disability within 2 weeks 5, 2, 6
• Diminished or absent reflexes (areflexia or hyporeflexia), typically beginning in the lower limbs 5, 1, 2
• Distal paresthesias or sensory loss often precede or accompany weakness 1
• History of recent infection (within 6 weeks) in approximately two-thirds of patients 1
• Back and limb pain affects approximately two-thirds of patients and can be an early symptom 1

Common Variants

• Classic sensorimotor GBS (30-85% of cases): rapidly progressive symmetrical weakness and sensory signs with absent or reduced tendon reflexes 5, 1
• Pure motor variant (5-70% of cases): motor weakness without sensory signs 5, 1
• Miller Fisher syndrome (5-25% of cases): ophthalmoplegia, ataxia, and areflexia 5, 1

Diagnostic Workup (Do Not Delay Treatment)

Obtain neurology consultation immediately for every suspected GBS case. 1, 2

Essential Laboratory Tests

• Complete blood count, glucose, electrolytes, kidney function, liver enzymes to exclude metabolic or electrolyte dysfunction 1
• Serum creatine kinase (CK)—elevation suggests muscle involvement and may indicate AMAN variant 1

Cerebrospinal Fluid Analysis

• Perform lumbar puncture to assess for albumino-cytological dissociation (elevated protein with normal cell count) 1, 2, 3
• Do NOT exclude GBS if CSF protein is normal during the first week of illness—protein elevation may not appear until after the first week 1, 3
• Marked CSF pleocytosis (significant white cell elevation) should prompt reconsideration of the diagnosis 1
• Also analyze CSF for cell count, differential, cytology, glucose, and cultures 1

Electrodiagnostic Studies

• Conduct nerve conduction studies and electromyography to support diagnosis and classify the neuropathy pattern (demyelinating vs. axonal) 1, 2, 3
• Look for the "sural sparing pattern": normal sural sensory nerve action potential with abnormal median/ulnar responses, which is typical for GBS 1
• Repeat electrodiagnostic studies in 2-3 weeks if initial studies are normal but clinical suspicion remains high—early studies may be normal within the first week 1

Imaging and Additional Testing

• MRI of spine with and without contrast to exclude compressive lesions and assess for nerve root enhancement/thickening 1
• Serum antiganglioside antibody testing (e.g., anti-GQ1b for Miller Fisher variant) 1, 3
• Do NOT delay immunotherapy while awaiting antibody test results—treatment should be initiated based on clinical suspicion 1, 3

First-Line Immunotherapy

Initiate treatment for any patient unable to walk unaided within 2-4 weeks of symptom onset. 1, 2, 3

Treatment Options (Equally Effective)

• IVIg 0.4 g/kg/day for 5 consecutive days (total dose 2 g/kg) 1, 2, 3
• Plasma exchange 200-250 ml/kg over 4-5 sessions 1, 2, 3

What NOT to Do

• Do NOT use corticosteroids alone for idiopathic GBS—they are ineffective 1, 3
• Do NOT use sequential plasma exchange followed by IVIg (or vice versa)—no additional benefit 1, 3
• Do NOT give a second IVIg course routinely to patients with poor prognosis—evidence does not support this 3

Expected Treatment Response and Complications

Approximately 40% of patients do not improve in the first 4 weeks after immunotherapy—this does NOT necessarily mean treatment failed, as progression might have been worse without therapy. 1, 3

Treatment-Related Fluctuations (TRFs)

• Occur in 6-10% of patients, defined as disease progression within 2 months after initial improvement or stabilization 1, 7, 3
• Repeating a full course of IVIg or plasma exchange is common practice for TRFs, although high-quality evidence is lacking 1, 3

Distinguishing GBS from Acute-Onset CIDP

• Consider reclassifying to acute-onset CIDP if progression continues after 8 weeks from onset or if the patient experiences ≥3 TRFs—this occurs in approximately 5% of patients initially diagnosed with GBS 1, 4, 3

Pain Management

Use gabapentinoids (gabapentin or pregabalin) or duloxetine for neuropathic pain—these can be started concurrently with IVIg without drug interaction. 1, 3

• Gabapentinoids, tricyclic antidepressants, or carbamazepine are weakly recommended for neuropathic pain 1, 3
• Encourage early mobilization for muscle pain and arthralgia 1

Medications to Avoid

Avoid drugs that impair neuromuscular transmission: β-blockers, intravenous magnesium, fluoroquinolones, aminoglycosides, and macrolides—they may exacerbate weakness. 1

Supportive Care

• Daily neurologic examinations to track disease progression 1
• Screen for anxiety, depression, and hallucinations, which are frequent complications 1
• Assess swallowing and coughing ability to identify aspiration risk 1
• Check corneal reflex in patients with facial palsy to prevent corneal ulceration 1
• Standard preventive measures for pressure ulcers, hospital-acquired infections, and deep vein thrombosis 1
• Treatment of constipation/ileus 1

Prognosis

Approximately 80% of patients regain independent walking ability at 6 months, with functional recovery continuing for several years and improvements reported beyond 5 years. 1, 2, 3, 6

Risk Factors for Poor Outcome

• Advanced age 1, 2, 3
• Severe disease at onset 1, 2, 3

Long-Term Sequelae

• Mortality is 3-10%, primarily from cardiovascular and respiratory complications 1, 2, 3, 6
• Fatigue affects 60-80% of survivors and is a major disabling symptom 1
• Severe pain persists in at least one-third of patients at 1 year and may continue for a decade or more 1
• Recurrence is uncommon (2-5% of patients) but higher than the background lifetime risk (0.1%) 1, 3

Rehabilitation

Arrange a structured rehabilitation program involving physiotherapists, occupational therapists, and rehabilitation specialists as soon as the patient is medically stable. 1

• Exercise programs (range-of-motion, stationary cycling, walking, strength training) improve physical fitness, walking ability, and independence in activities of daily living 1
• Monitor exercise intensity to avoid fatigue 1

Special Situation: Immune Checkpoint Inhibitor-Associated GBS

• Permanently discontinue the immune checkpoint inhibitor when GBS is diagnosed 1
• Add concurrent corticosteroids (methylprednisolone 2-4 mg/kg/day) to IVIg or plasma exchange in this context 1
• For Grade 3-4 severity, pulse corticosteroid therapy (methylprednisolone 1 g/day for 5 days) can be employed as an adjunct 1

Common Pitfalls

• Do NOT dismiss GBS based on normal CSF protein in the first week—protein elevation may develop later 1, 3
• Do NOT wait for antibody results before starting treatment—approximately 63% of GBS patients lack detectable antiganglioside antibodies 1
• Do NOT assume normal reflexes rule out GBS—pure motor variant and AMAN subtype can have normal or even exaggerated reflexes 4
• Do NOT diagnose GBS too quickly in slowly progressive cases—progression >4 weeks should raise suspicion for CIDP 4
• Bilateral simultaneous facial weakness is extremely rare in Bell's palsy and should immediately raise suspicion for GBS 1