Guillain-Barré Syndrome (GBS)

Overview

Pathophysiology

• Campylobacter jejuni (most common bacterial trigger — associated with axonal subtypes via GM1 ganglioside antibodies)
• Epstein-Barr virus, CMV, HIV, Zika virus, SARS-CoV-2
• Vaccines (rare association)

Subtypes (Box 106.11 — Bradley & Daroff's Neurology)

Clinical Features

• Ascending symmetrical weakness beginning in the lower limbs, spreading proximally over hours to days
• Areflexia/hyporeflexia — invariable feature (may be absent very early)
• Paresthesias in hands and feet — sensory loss is usually mild
• Progression peaks by 4 weeks (most reach nadir by 2–4 weeks)

• Bilateral facial paresis in ≥50%
• Extraocular muscle involvement (especially in MFS)
• Lower cranial nerve palsies (dysphagia, dysarthria)

• Orthostatic hypotension, urinary retention, GI atony
• Tachyarrhythmias, sinus tachycardia
• Bradycardia, heart block, asystole from vagal spells (can be triggered by tracheal suctioning)
• ECG changes: T-wave abnormalities, ST depression, QT prolongation, heart block

Diagnosis

Required Features (Asbury & Cornblath Criteria)

1. Progressive weakness of both legs and arms
2. Areflexia or hyporeflexia

Supportive Clinical Features

• Progression over days to ≤4 weeks
• Relative symmetry
• Mild sensory symptoms
• Bifacial palsies
• Autonomic dysfunction
• Absence of fever at onset
• Recovery beginning 2–4 weeks after progression ceases

Laboratory/Investigation Findings

Treatment

Disease-Modifying Therapy

1. Intravenous Immunoglobulin (IVIg) — 0.4 g/kg/day × 5 days (most widely used; suppresses immune response via multiple mechanisms)
2. Plasmapheresis (plasma exchange) — removes offending antibodies; equally effective to IVIg; typically 5 exchanges over 2 weeks
3. Combination of both offers no additional benefit over either alone
4. Corticosteroids — NOT effective (do not alter outcome; may worsen it)

Supportive Care

• Respiratory monitoring: Forced vital capacity (FVC) every 4–6 hrs; intubate if FVC <15–20 mL/kg, rapid decline, or bulbar compromise ("20-30-40 rule")
• Cardiac monitoring (continuous ECG) for autonomic dysfunction
• DVT prophylaxis (subcutaneous heparin + compression stockings)
• Nutrition, pain management (gabapentin, carbamazepine, opioids)
• Physiotherapy and rehabilitation

Prognosis

• Mortality: ~1–5% (down from 33% before positive-pressure ventilation was introduced)
• Most patients recover over weeks to months
• ~15–20% have residual significant disability at 1 year
• Poor prognostic factors: older age, rapid onset, requirement for ventilation, severe axonal involvement, C. jejuni preceding infection, low CMAP amplitude

Key Differentials

Reactive Arthritis (ReA)

Definition

Arthritis + Urethritis/Cervicitis + Conjunctivitis

Epidemiology

• Global prevalence: ~30 per 100,000 adults
• Predominantly affects young adults (20–40 years)
• More commonly diagnosed in men (genitourinary trigger) though GI-triggered cases affect men and women equally
• HLA-B27 is present in the majority; B27-positive individuals have a 20% risk of developing ReA after Salmonella or Yersinia epidemics (vs. 2–7% in B27-negative)

Triggering Pathogens

Pathobiology

• Bacterial antigens have been identified in joints by immunofluorescence after both GI and GU infections
• PCR studies are most consistently positive in post-Chlamydia ReA, suggesting viable Chlamydia may persist in joint tissue in a metabolically altered state
• Toll-like receptor 2 (TLR-2) genetic variants implicate innate immune dysregulation in susceptibility
• Both T cell–mediated and antibody-mediated mechanisms are involved
• Dactylitis results from inflammation of the joint capsule, entheses, periarticular structures, and periosteal bone collectively

Clinical Features

Articular

• Asymmetric oligoarthritis of lower extremities (knee most common)
• Predilection for large joints; waxing/waning course
• Enthesitis: Achilles tendinitis, plantar fasciitis → heel pain and swelling
• Dactylitis: "sausage digit" — synovitis of a digital tendon sheath; may progress to calcaneal spurs and bony outgrowths
• Sacroiliitis: typically asymmetrical (distinguishes from ankylosing spondylitis, which is symmetrical)
• In chronic disease: bulky, non-marginal, asymmetrical syndesmophytes (vs. the thin marginal syndesmophytes of AS)
• Inflammatory low back pain is a common accompaniment

Extra-articular Features

Diagnosis

Key differential: Septic arthritis — both Yersinia and Salmonella can cause true septic arthritis. Synovial fluid culture must be obtained before diagnosing reactive arthritis.

Treatment

Step 1 — Treat the Triggering Infection

• Post-Chlamydia ReA: 6-month course of combination antibiotic therapy:
  • Rifampicin 300 mg/day + doxycycline 100 mg twice daily or azithromycin (500 mg twice daily × 5 days, then 500 mg/week)
  • Response rate 65% (vs. ~20% with placebo); complete remission in 20% (vs. 0%)
• Appropriate antibiotic treatment for GI triggers if indicated

Step 2 — Anti-inflammatory Therapy

• NSAIDs — first-line for joint symptoms and enthesitis
• Glucocorticoid injections — effective for individual joint or enthesis involvement
• Sulfasalazine — recommended in more severe cases, especially if started within the first 3 months; more efficacious than methotrexate for this condition

Step 3 — Refractory / Chronic Disease

• Anti-TNF agents (infliximab, etanercept, adalimumab) — used in chronic HLA-B27-positive spondyloarthritis, though evidence specifically for ReA is limited
• Note: ~50% of patients recover within 6 months, so aggressive biologic use must be weighed carefully

Prognosis

• ~50% recover within 6 months
• ~50% have recurrent arthritis, tendinitis, or lumbosacral pain
• Risk of progression to chronic spondyloarthritis / ankylosing spondylitis exists (frequency not precisely defined)
• HLA-B27 positivity confers risk for axial involvement and chronicity
• HIV co-infection: more aggressive, refractory course

Investigation of Choice — Reactive Arthritis

1. Most Important Test: Synovial Fluid Analysis (Arthrocentesis)

• Purpose: To exclude septic arthritis — the most critical differential
• Findings in ReA: inflammatory fluid (WBC 2,000–50,000/μL, predominantly neutrophils), sterile on culture
• Both Yersinia and Salmonella can cause true septic arthritis, so synovial fluid must be cultured before diagnosing ReA

⚠️ Culture of synovial fluid must precede the diagnosis of reactive arthritis whenever possible (Goldman-Cecil Medicine).

2. HLA-B27 Testing

• Positive in the majority of patients
• Not diagnostic on its own, but:
  • Guides prognosis (B27+ → higher risk of axial involvement, chronicity, sacroiliitis)
  • B27+ individuals have up to 20% risk of ReA after epidemic GI infection (vs. 2–7% in B27−)

3. Identify the Triggering Infection

4. Radiology (Supportive, Not Diagnostic)

• X-ray of affected joints: juxta-articular osteopenia, periosteal new bone, enthesophytes
• X-ray of sacroiliac joints: asymmetric sacroiliitis (distinguishes from ankylosing spondylitis, which is symmetric)
• Not first-line for diagnosis but useful for staging and ruling out other causes

5. Non-Specific Inflammatory Markers

• ESR, CRP — elevated but non-specific
• CBC: leukocytosis
• Useful for monitoring disease activity, not diagnosis

Summary Table