Guillain-Barré Syndrome (GBS)

1. DEFINITION AND EPIDEMIOLOGY

• Males are at slightly higher risk than females
• In Western countries, adults are more frequently affected than children

2. SUBTYPES (Table 458-1)

3. ANTECEDENT EVENTS / TRIGGERS

• Campylobacter jejuni - 20-30% of cases (North America, Europe, Australia); also summer outbreaks of AMAN in rural China
• Human herpesvirus (CMV, EBV) - similar proportion
• HIV, Hepatitis E, Zika virus, Mycoplasma pneumoniae
• SARS-CoV-2 - reported cases but causal relationship not established
• Vaccines: Swine influenza vaccine (1976) is the most notable example; recent seasonal influenza vaccines carry <1 per million risk; SARS-CoV-2 adenovirus-vector vaccines have increased risk; mRNA vaccines do not; old rabies vaccines (nervous tissue-derived) in developing countries

4. CLINICAL MANIFESTATIONS

Motor Features

• Rapidly evolving areflexic motor paralysis with or without sensory disturbance
• Classic ascending paralysis - "rubbery legs" first
• Weakness evolves over hours to a few days
• Legs more affected than arms
• Facial paresis in 50%
• Lower cranial nerve involvement (bulbar weakness, difficulty handling secretions, airway compromise) - may mimic brainstem ischemia
• ~30% require mechanical ventilation

Sensory Features

• Tingling dysesthesias in extremities
• Cutaneous sensory deficits (pain, temperature) relatively mild
• Large fiber functions (DTRs, proprioception) more severely affected

Reflexes

• Deep tendon reflexes attenuate or disappear within the first few days

Autonomic Involvement

• Common even in mild GBS
• Loss of vasomotor control with wide fluctuations in BP
• Postural hypotension, hypertension
• Cardiac dysrhythmias
• Can be life-threatening

Pain

• Present in ~50% of patients early on
• Deep aching pain in weakened muscles ("overexercised the previous day")
• Dysesthetic pain in extremities (sensory nerve fiber involvement)
• Pain in neck, shoulder, back, or diffusely over the spine

Bladder Dysfunction

• May occur in severe cases; usually transient
• If prominent/early - consider other diagnoses (spinal cord disease)

Fever

• Absent at onset - if present, casts doubt on the diagnosis

Plateau Phase

• Once worsening stops, plateau almost always reached within 4 weeks of onset

5. IMMUNOPATHOGENESIS

• Most cases are triggered by a preceding infection that induces immune response against peripheral nervous system gangliosides via molecular mimicry
• C. jejuni lipooligosaccharide bears ganglioside-like epitopes - antibodies cross-react with nerve antigens
• In AMAN: IgG anti-GM1 or anti-GD1a autoantibodies bind to the nodal axolemma, leading to MAC (membrane attack complex) formation
• This causes disappearance of Nav channel clusters and detachment of paranodal myelin - nerve conduction failure and muscle weakness
• Axonal degeneration and macrophage invasion of the periaxonal space follow

• Anti-GM1, anti-GD1a - AMAN/AMSAN
• Anti-GQ1b - Miller Fisher Syndrome (strongly associated)
• Anti-GM2 - GBS with bulbar/facial palsy + CMV

6. ELECTRODIAGNOSTICS (EDx)

• Findings vary with subtype: AIDP shows demyelinating pattern; AMAN/AMSAN show axonal pattern
• Abnormal findings may not be present in the first week
• Treatment should not wait for EDx confirmation if diagnosis strongly suspected

7. CSF FINDINGS

• Elevated CSF protein above normal
• CSF WBC count <10 cells/μL (acellular or very few cells)
• Protein rises progressively in the first few weeks
• CSF pleocytosis should prompt HIV testing

8. DIAGNOSTIC CRITERIA (Sejvar et al., updated; reproduced in Harrison's 22e)

For GBS (Limb Weakness Form):

• Bilateral AND flaccid weakness of the limbs
• Decreased or absent DTRs in weak limbs
• Monophasic illness; onset to nadir: 12 hours - 28 days; then plateau
• EDx consistent with GBS
• Cytoalbuminologic dissociation (elevated CSF protein + WBC <50 cells/uL)
• No alternative diagnosis

• Same motor/reflex criteria + monophasic course
• CSF WBC <50 (with/without protein elevation) OR EDx consistent with GBS
• No alternative diagnosis

• Bilateral flaccid limb weakness + decreased/absent DTRs + monophasic course
• No alternative diagnosis (CSF/EDx not required)

For Miller Fisher Syndrome:

9. DIFFERENTIAL DIAGNOSIS

• Brainstem ischemia (when bulbar/facial involvement prominent)
• Spinal cord disease (when early/prominent bladder dysfunction or sensory level)
• Other causes of acute flaccid paralysis

10. TREATMENT

Immunotherapy (initiate as soon as possible):

• Usually first choice (ease of administration, good safety record)
• Dose: 2 g/kg total given as 5 daily infusions (0.4 g/kg/day)
• Mechanism: GBS autoantibodies may be neutralized by anti-idiotypic antibodies in IVIg

• 4-6 exchanges of ~40-50 mL/kg over 7-12 days
• Meta-analysis: reduces need for mechanical ventilation from 27% to 14%; increases full recovery at 1 year from 55% to 68%

• Treatment should be initiated within 2 weeks of first motor symptoms (efficacy uncertain after that)
• If patient has reached plateau - treatment generally not indicated unless severe weakness and active immunologic attack cannot be excluded
• If patient improves then relapses within a month - brief retreatment with original therapy is usually effective
• Glucocorticoids are NOT effective in GBS
• Mild GBS patients who have already plateaued may be managed conservatively

Critical Care:

• ~30% need ventilatory support
• Monitor: vital capacity, heart rhythm, BP, nutrition, DVT prophylaxis
• Early tracheotomy consideration (after 2 weeks of intubation)
• Chest physiotherapy, skin care, range-of-motion exercises
• Daily reassurance (generally good prognosis)

Symptomatic:

• Pain: standard analgesics (self-limited)

11. PROGNOSIS AND RECOVERY

• ~85% achieve full functional recovery within several months to a year
• Minor findings (areflexia) may persist; fatigue complaints common
• Mortality <5% in optimal settings; death usually from secondary pulmonary complications
• Worst prognosis: severe proximal motor/sensory axonal damage
• Poor prognostic factors:
  • Advanced age
  • Fulminant or severe attack
  • Delay in treatment onset
  • Elevated serum neurofilament light (NfL) chains
  • High titers of serum anti-GM1 antibodies
• 5-10% have one or more late relapses - many then reclassified as CIDP (Chronic Inflammatory Demyelinating Polyneuropathy)

12. GBS vs. CIDP (Key Distinction)

Summary for Exam

1. Ascending flaccid paralysis + areflexia - hallmark presentation
2. Albuminocytologic dissociation in CSF - signature finding
3. C. jejuni is the most common antecedent infection (20-30%)
4. AIDP = most common subtype; MFS = anti-GQ1b (ophthalmoplegia + ataxia + areflexia)
5. IVIg (2g/kg over 5 days) = PLEX - both equally effective; NO steroids
6. 30% need ventilation - watch vital capacity
7. 85% full recovery; <5% mortality
8. Treat within 2 weeks of onset; plateau within 4 weeks
9. Pain in 50%, autonomic dysfunction common
10. Late relapses (5-10%) → reclassify as CIDP