What is the treatment for Guillain-Barré Syndrome (GBS)?

Guillain-Barré Syndrome: Comprehensive Overview

Definition and Epidemiology

Guillain-Barré syndrome is an acute immune-mediated inflammatory disease of the peripheral nervous system causing rapidly progressive bilateral weakness that requires immediate recognition and treatment, with a mortality rate of 3-10% even with optimal care. 1, 2

• Annual global incidence is approximately 1-2 per 100,000 person-years, occurring more frequently in males and with increasing age 2
• GBS is the most common cause of acute flaccid paralysis worldwide 2, 3
• Approximately 20% of patients develop respiratory failure requiring mechanical ventilation, which can occur rapidly and sometimes without obvious dyspnea 2, 4
• About 25% of patients require artificial ventilation during the disease course 5

Clinical Presentation

Classic Features

• Rapidly progressive bilateral weakness starting in the legs and ascending to arms and cranial muscles is the hallmark presentation 1, 2
• Distal paresthesias or sensory loss typically accompany or precede weakness 1, 2
• Decreased or absent reflexes are present in most patients at presentation and almost all at nadir 1, 2
• Disease progression typically reaches maximum disability within 2 weeks of onset 1, 4
• Patients who reach maximum disability within 24 hours or after 4 weeks should prompt consideration of alternative diagnoses 1

Associated Symptoms

• Pain (muscular, radicular, or neuropathic) is frequently reported and can be severe 1, 2
• Dysautonomia occurs commonly, including blood pressure/heart rate instability, pupillary dysfunction, and bowel/bladder dysfunction 1, 2
• Cardiac arrhythmias from autonomic involvement can be life-threatening 2, 4
• Pain can precede weakness and cause diagnostic confusion 5

Atypical Presentations

• Weakness can be asymmetrical or predominantly proximal/distal, starting in legs, arms, or simultaneously 1
• Severe diffuse pain or isolated cranial nerve dysfunction can precede weakness 1
• Young children (<6 years) may present with poorly localized pain, refusal to bear weight, irritability, meningism, or unsteady gait 1
• Pure motor variant may show normal or even exaggerated reflexes, particularly in AMAN subtype 1

Clinical Variants

• Pure motor variant: weakness without sensory signs 1, 2
• Miller Fisher syndrome (MFS): ophthalmoplegia, areflexia, and ataxia 1, 2, 6
• Regional variants: bilateral facial palsy with paresthesias, pharyngeal-cervical-brachial weakness, or paraparetic variant (lower limbs only) 1, 2
• Overlap syndromes: GBS-MFS overlap exists 5

Diagnostic Approach

Clinical Diagnosis

The diagnosis of GBS is primarily clinical, supported by cerebrospinal fluid analysis and electrophysiological studies. 2, 6

• Ascending bilateral symmetric weakness (legs → arms → cranial nerves) strongly suggests GBS 2
• Areflexia or hyporeflexia in affected limbs points to GBS 2
• History of recent diarrhea or respiratory infection increases likelihood 6

Laboratory Investigations

• CSF analysis typically shows elevated protein with normal cell count (albumino-cytological dissociation), though not all patients demonstrate this finding 2, 6, 7
• CSF examination is particularly valuable when diagnosis is uncertain 6
• Electrophysiological studies (nerve conduction studies and EMG) provide evidence of peripheral nerve dysfunction and help differentiate subtypes 2, 6
• Anti-GQ1b antibody testing should be considered when Miller Fisher syndrome is suspected 6
• Testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS 6
• Nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected 6

Imaging

• MRI or ultrasound imaging should be considered in atypical cases 6
• MRI of spine with/without contrast can rule out compressive lesions and evaluate for nerve root enhancement/thickening 1

Respiratory and Cardiac Monitoring

• Vital capacity and negative inspiratory force should be assessed to evaluate respiratory function 2
• Continuous monitoring for cardiac arrhythmias and blood pressure instability is critical 1, 2
• Frequent pulmonary function assessment is essential, as respiratory failure can occur rapidly 1

Differential Diagnosis

Key Distinguishing Features

• Descending flaccid paralysis (cranial nerves → trunk → extremities) indicates botulism until proven otherwise 2
• Normal or preserved reflexes with flaccid paralysis suggests botulism or myasthenia gravis 2
• Progression beyond 4 weeks should prompt consideration of alternative diagnoses including acute-onset CIDP 1, 6

Important Mimics (Particularly in Low-Resource Settings)

• Acute flaccid myelitis due to infections (Zika virus, chikungunya, West Nile virus, polio, enterovirus) 1
• Poly(radiculo)neuritis from HIV, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, diphtheria, or Lyme disease 1
• Botulism or tetanus 1
• Electrolyte disorders (hypokalaemia, hypophosphataemia, hypermagnesaemia) 1
• Toxins (organophosphates, lead, thallium, arsenic) 1
• Acute transverse myelitis 1
• Myasthenia gravis 1

Treatment

Immunotherapy

Intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 days (total dose 2 g/kg) or plasma exchange are equally effective first-line treatments for patients unable to walk unaided. 1, 4, 6

• IVIg is recommended for patients within 2 weeks after onset of weakness if unable to walk unaided 6
• IVIg can also be considered within 2-4 weeks after onset 6
• Plasma exchange (200-250 ml/kg for 5 sessions or 12-15 L in 4-5 exchanges over 1-2 weeks) is recommended for patients within 4 weeks after onset if unable to walk unaided 1, 6
• Early treatment (within the first 2 weeks) is associated with better outcomes 4
• IVIg is generally preferred as first choice because it is easy to administer, widely available, and associated with fewer adverse effects compared to plasma exchange 1
• Plasma exchange is less costly than IVIg and could be preferred in resource-limited settings, though practical limitations exist 1

What NOT to Do

• Do not use oral corticosteroids - they are ineffective and not recommended 6, 8
• Do not use IV corticosteroids alone - weakly recommended against 6
• Do not perform plasma exchange followed immediately by IVIg - not recommended 6
• Do not routinely give a second IVIg course in GBS patients with poor prognosis - recommended against 6

Treatment of Complications

Pain Management

• Gabapentinoids, tricyclic antidepressants, or carbamazepine are weakly recommended for neuropathic pain 6
• Nonopioid management of neuropathic pain is preferred 1
• Pregabalin, gabapentin, or duloxetine can be used 1

Respiratory Management

• Approximately 20% require mechanical ventilation 2, 4
• Admission to inpatient unit with capability for rapid transfer to ICU-level monitoring is essential for severe cases 1
• Use modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess risk of requiring artificial ventilation 6

Autonomic Dysfunction

• Monitor for arrhythmias, blood pressure shifts, and respiratory distress caused by mucus plugs 1
• Monitoring is especially important in patients who have recently left ICU and those with cardiovascular risk factors 1
• Avoid medications that can worsen autonomic dysfunction 1

Other Complications

• Standard preventive measures for pressure ulcers, hospital-acquired infections, and deep vein thrombosis 1
• Manage inability to swallow safely in patients with bulbar palsy 1
• Prevent corneal ulceration in patients with facial palsy 1
• Address limb contractures, ossification, and pressure palsies 1
• Recognize and treat pain, hallucinations, anxiety, and depression early 1
• Multidisciplinary team involvement (nurses, physiotherapists, rehabilitation specialists, occupational therapists, speech therapists, dietitians) is essential 1

Special Clinical Scenarios

Treatment-Related Fluctuations (TRFs)

• TRFs occur in 6-10% of patients, defined as disease progression within 2 months following initial treatment-induced improvement or stabilization 1, 4
• TRFs indicate treatment effect has worn off while inflammatory phase continues 1
• Repeating the full course of IVIg or plasma exchange is common practice, though evidence is lacking 1

Insufficient Response to Treatment

• About 40% of patients treated with standard doses do not improve in first 4 weeks 1
• Disease progression does not necessarily imply treatment is ineffective 1
• Evidence for repeating treatment or changing to alternative treatment is lacking 1

Acute-Onset CIDP

• In ~5% of patients, repeated clinical relapses suggest chronic disease process 1
• Diagnosis is changed to acute-onset CIDP when there are three or more TRFs and/or clinical deterioration ≥8 weeks after disease onset 1, 6

Immune Checkpoint Inhibitor-Related GBS

Grading and Management

For immune checkpoint inhibitor-related GBS, all grades warrant workup and intervention given potential for progressive disease leading to respiratory compromise. 1

Grade 2 (Moderate)

• Discontinue immune checkpoint inhibitor 1
• Neurology consultation required 1

Grade 3-4 (Severe)

• Permanently discontinue immune checkpoint inhibitor 1
• Admission to inpatient unit with ICU-level monitoring capability 1
• Start IVIg (0.4 g/kg/day for 5 days, total 2 g/kg) or plasmapheresis 1
• Corticosteroids (methylprednisolone 2-4 mg/kg/day) are reasonable in immune checkpoint inhibitor-related forms, though not typically used for idiopathic GBS 1
• Pulse steroid dosing (methylprednisolone 1 g daily for 5 days) may be considered for grade 3-4 along with IVIg or plasmapheresis 1
• Frequent neuro checks and pulmonary function monitoring required 1
• Monitor for concurrent autonomic dysfunction 1

Prognosis

Short-Term Outcomes

• About 60-80% of patients are able to walk independently 6 months after disease onset 1, 4
• Use modified Erasmus GBS outcome score (mEGOS) on admission to calculate probability of regaining walking ability 1, 6
• Death occurs in 3-10% of cases, most commonly from cardiovascular and respiratory complications 1, 2
• Risk factors for mortality include advanced age and severe disease at onset 1

Long-Term Recovery

• Most patients show extensive recovery, especially in the first year after disease onset 1
• Even patients who were tetraplegic at nadir or required prolonged mechanical ventilation can show extensive recovery 1
• Recovery can continue >3-5 years after disease onset 1
• About 20% of patients are still unable to walk after 6 months 5
• Long-term residual complaints are common, including neuropathic pain, weakness, and fatigue 1

Recurrence

• Recurrent episodes of GBS are rare, affecting 2-5% of patients 1, 5

Critical Pitfalls to Avoid

• Do not dismiss early symptoms: Pain, refusal to bear weight in children, or isolated cranial nerve dysfunction can precede weakness 1
• Do not assume dyspnea will be present: Respiratory failure can occur rapidly without obvious dyspnea 2, 4
• Do not overlook autonomic dysfunction: Cardiac arrhythmias and blood pressure instability can be life-threatening 2, 4
• Do not delay treatment: Early immunotherapy (within first 2 weeks) is associated with better outcomes 4
• Do not use corticosteroids alone: They are ineffective in GBS 6, 8
• Do not forget that patients have intact consciousness: Even those with complete paralysis usually have intact consciousness, vision, and hearing - be mindful of bedside conversations 1
• Do not miss alternative diagnoses: If progression continues beyond 4 weeks or patient has multiple relapses, consider acute-onset CIDP 1, 6