What is the treatment for Guillain Barre Syndrome (GBS)?

Guillain-Barré Syndrome: Comprehensive Overview

Definition and Epidemiology

Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory disease of the peripheral nervous system and the most common cause of acute flaccid paralysis worldwide. 1 The annual global incidence is approximately 1-2 per 100,000 person-years, with males affected more frequently than females and incidence increasing with age, though all age groups can be affected. 1

Pathophysiology

GBS is triggered by an aberrant immune response to preceding infections that results in damage to peripheral nerves through molecular mimicry. 1 In a subgroup of patients, serum antibodies against gangliosides (which reside at high densities in the axolemma) are found, with complement activation, macrophage infiltration, and edema being typical characteristics of affected peripheral nerves and nerve roots. 1 Common antecedent pathogens include Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumoniae. 2 The incidence of GBS can increase during outbreaks of infectious diseases, as demonstrated during the Zika virus epidemics in French Polynesia (2013) and Latin America (2015-2016). 1

Clinical Presentation

Classic Features

• Ascending weakness and sensory signs typically beginning in the legs and progressing to the arms and cranial muscles, though clinical presentation is heterogeneous. 1
• Rapid disease progression with most patients reaching maximum disability within 2 weeks. 1
• Respiratory failure develops in approximately 20% of patients, requiring mechanical ventilation. 1
• Autonomic dysfunction including cardiac arrhythmias and blood pressure instability can occur and contributes significantly to mortality. 1

Disease Course

The disease follows a monophasic pattern with three phases: 1

• Progressive phase: Rapid worsening over days to 2 weeks
• Plateau phase: Lasting days to weeks or months
• Recovery phase: 60-80% of patients can walk independently at 6 months 1

Treatment-related fluctuations (TRFs) occur in 6-10% of patients within 2 months of initial improvement, representing disease reactivation while the inflammatory phase continues. 3, 4 Relapses can occur in 2-5% of patients, and approximately 5% of cases initially diagnosed as GBS may actually represent acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) if repeated relapses occur. 1, 3

Clinical Subtypes

Electrophysiological studies distinguish between three main subtypes: 1

• Acute inflammatory demyelinating polyradiculoneuropathy (AIDP): Most common in Europe and North America
• Acute motor axonal neuropathy (AMAN): More frequent in East Asia
• Acute motor sensory axonal neuropathy (AMSAN): Severe variant with both motor and sensory involvement

Miller Fisher syndrome is a distinct variant characterized by ataxia, ophthalmoplegia, and areflexia, associated with anti-GQ1b antibodies. 1

Diagnosis

Clinical Evaluation

Diagnosis is based on patient history, neurological examination, electrophysiological studies, and cerebrospinal fluid (CSF) analysis. 1 A history of recent diarrhea or respiratory infection increases the likelihood of GBS. 5

Diagnostic Testing

• CSF examination: Classic finding is elevated protein with normal cell count (albuminocytologic dissociation), though this may be normal early in the disease course. 1 In immune checkpoint inhibitor-associated cases, CSF may show elevated white blood cells. 1
• Electrophysiological studies: Provide evidence of peripheral nervous system dysfunction and help distinguish between GBS subtypes. 1
• Anti-ganglioside antibody testing: Of limited clinical value in typical motor-sensory GBS, but anti-GQ1b testing should be considered when Miller Fisher syndrome is suspected. 5
• MRI of spine with and without contrast: To rule out compressive lesions and evaluate for nerve root enhancement/thickening. 1

Differential Diagnosis

Critical alternative diagnoses to exclude include: 1

• Acute transverse myelitis and other inflammatory myelopathies
• Brainstem or spinal cord stroke
• Compressive lesions (tumor, cauda equina syndrome)
• Infectious causes (poliomyelitis, West Nile virus, enterovirus D68, HIV, cytomegalovirus)
• Metabolic disorders (hypokalemia, hypophosphatemia, porphyria, vitamin B12 deficiency)
• Toxins (organophosphates, lead, arsenic)
• Myasthenia gravis
• Botulism
• Critical illness polyneuropathy

Treatment

First-Line Immunotherapy

Intravenous immunoglobulin (IVIg) at 0.4 g/kg body weight daily for 5 consecutive days is the preferred first-line treatment for any patient with GBS who cannot walk unaided. 4 Treatment should be initiated as early as possible, ideally within 2 weeks of symptom onset. 4 IVIg is preferred over plasma exchange because it is easier to administer, more widely available, has higher completion rates, and better tolerability with fewer complications—particularly important in children and pregnant women. 3, 4

Plasma exchange (200-250 ml/kg in 4-5 sessions over 1-2 weeks) is equally effective and should be used when IVIg is contraindicated, not tolerated, or unavailable. 1, 4 Plasma exchange may be preferred in low- and middle-income countries due to lower cost (~$4,500-5,000 vs. $12,000-16,000 for IVIg), though availability and technical requirements can be limiting factors. 1

Treatments NOT Recommended

• Corticosteroids alone are NOT recommended as they have shown no significant benefit and may have negative effects on outcomes. 3, 5
• Plasma exchange followed immediately by IVIg is NOT recommended as plasma exchange will remove the administered immunoglobulin. 5
• A second course of IVIg in patients with poor prognosis is NOT recommended based on current evidence. 5

Managing Treatment Failures and Fluctuations

For treatment-related fluctuations (occurring in 6-10% of patients), repeat the full course of IVIg or switch to plasma exchange, though evidence supporting this approach is limited. 3, 4 Approximately 40% of patients do not show improvement in the first 4 weeks following treatment, which doesn't necessarily indicate treatment ineffectiveness. 3

Critical Care Management

ICU Admission Criteria

Admit to ICU if any of the following are present: 4

• Evolving respiratory distress with imminent respiratory insufficiency
• Severe autonomic cardiovascular dysfunction
• Severe swallowing dysfunction or diminished cough reflex
• Rapid progression of weakness

Respiratory Monitoring

Apply the "20/30/40 rule" to identify patients at imminent risk of respiratory failure: 3, 4

• Vital capacity <20 ml/kg
• Maximum inspiratory pressure <30 cmH₂O
• Maximum expiratory pressure <40 cmH₂O

Single breath count ≤19 predicts need for mechanical ventilation. 3, 4 Regular assessment should include monitoring for use of accessory respiratory muscles and evaluation of swallowing and coughing ability to prevent aspiration. 3

Autonomic Monitoring

Continuous ECG monitoring for arrhythmias, blood pressure monitoring for hypertension/hypotension, and monitoring of bowel and bladder function are essential. 4 Autonomic dysfunction contributes significantly to the 3-10% mortality rate even with optimal medical care. 1, 4

Supportive Care and Complication Management

Pain Management

Pain is common in GBS and significantly impacts quality of life—recognize and treat early. 4 For neuropathic pain, gabapentinoids, tricyclic antidepressants, or carbamazepine are weakly recommended. 5 Use nonopioid management strategies when possible. 1

Prevention of Complications

• Pressure ulcer prevention through regular repositioning 3
• Deep vein thrombosis prophylaxis 3
• Prevention of hospital-acquired infections 3
• Treatment of constipation/ileus 1

Psychological Support

Psychological support for anxiety, depression, and hallucinations is crucial as these are frequent in GBS patients. 3

Rehabilitation

Initiate early rehabilitation with a multidisciplinary team including physiotherapists, occupational therapists, speech therapists, and dietitians. 4 The program should include range-of-motion exercises, stationary cycling, walking, and strength training to improve physical fitness and independence in activities of daily living. 3, 4 Monitor exercise intensity closely as overwork can cause fatigue. 3, 4

Prognosis

Short-Term Outcomes

• 80% of patients regain independent walking ability at 6 months 4
• Mortality is 3-10%, primarily from cardiovascular and respiratory complications, with up to two-thirds of deaths occurring during the recovery phase 1, 3, 4
• Risk factors for mortality include advanced age and severe disease at onset 4

Long-Term Outcomes

Long-term residual complaints can include neuropathic pain, weakness, and fatigue, but recovery may still occur >5 years after disease onset. 3 Many patients have persistent pain and fatigue that can last for months or years. 1

Prognostic Tools

Use the modified Erasmus GBS outcome score (mEGOS) to assess outcome and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. 5

Special Considerations

Immune Checkpoint Inhibitor-Associated GBS

For patients developing GBS as an immune-related adverse event from cancer immunotherapy, management differs slightly: 1

• Discontinue immune checkpoint inhibitor
• Start IVIG (0.4 g/kg/day for 5 days) or plasmapheresis
• Consider pulse steroids (methylprednisolone 1-2 g daily for 5 days) in addition to IVIG or plasmapheresis for grade 3-4 cases 1
• Extreme caution with rechallenge after complete resolution 1

Pediatric Considerations

In children, IVIg is the preferred first-line therapy due to better tolerability and fewer complications compared to plasma exchange. 3 For RSV-associated GBS, consider palivizumab prophylaxis during RSV season and Pneumocystis pneumonia prophylaxis with trimethoprim/sulfamethoxazole. 3

Common Pitfalls

• Do not wait for CSF or electrophysiological confirmation before initiating treatment if clinical suspicion is high, as both tests can be normal early in the disease course. 1
• Do not underestimate respiratory risk—respiratory failure can occur without symptoms of dyspnea. 1
• Avoid medications that can worsen neuromuscular transmission: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides. 1
• Do not assume lack of improvement at 4 weeks indicates treatment failure—this is common and doesn't necessarily warrant additional intervention. 3
• Consider A-CIDP if progression continues beyond 8 weeks from onset, as this occurs in approximately 5% of patients initially diagnosed with GBS and requires different long-term management. 3, 5