Guillain-Barre Syndrome (GBS)

Definition

GBS refers to a group of acquired, acute-onset inflammatory polyradiculoneuropathies characterized by:

Progressive limb weakness
Areflexia or hyporeflexia
Elevated CSF protein with low cell count (albuminocytological dissociation / cytoalbuminologic dissociation)
Monophasic course

It is the leading cause of acute flaccid paralysis in Western countries following the eradication of poliomyelitis.

Goldman-Cecil Medicine, p. 4080; Bradley and Daroff's Neurology in Clinical Practice, p. 2663

Epidemiology

Annual incidence: 1-2 per 100,000
Male : Female ratio = 1.4-1.5 : 1
Affects all ages; incidence rises with age (0.8 per 100,000 in <18 years to 3.2 per 100,000 in >60 years)
60% of cases are preceded by a respiratory or GI infection
Campylobacter jejuni diarrhea is the most common identified preceding infection, especially in axonal variants
Zika virus is significantly associated with GBS
SARS-CoV-2 infection or vaccination does not appear substantially associated with GBS, except a slight increase (0.6/100,000 doses) with the ChADOx1 (AstraZeneca) vaccine

Subtypes & Variants (Classification)

Subtype	Key Features
AIDP (Acute Inflammatory Demyelinating Polyneuropathy)	Most common in Europe/North America (97%); demyelinating pattern on NCS
AMAN (Acute Motor Axonal Neuropathy)	Pure motor; first described in northern China; summer epidemics in children
AMSAN (Acute Motor-Sensory Axonal Neuropathy)	Both motor and sensory axons; more severe; poor recovery
Miller-Fisher Syndrome (MFS)	Triad: ophthalmoplegia + ataxia + areflexia; GQ1b antibodies >85%; normal NCS
Pharyngeal-cervical-brachial variant	Bulbar/arm weakness
Acute pandysautonomia	Predominant autonomic involvement
Facial diplegia with paresthesias	Bilateral facial weakness + sensory symptoms

Pathophysiology

All forms likely result from postinfectious molecular mimicry: the immune system attacks peripheral nerve antigens that resemble microbial antigens (particularly C. jejuni). In AIDP:

Endoneurial perivascular mononuclear cell infiltration
Multifocal demyelination of spinal roots and peripheral nerves (most at ventral roots, proximal spinal nerves, lower cranial nerves)
Macrophages strip myelin lamellae from axons
Infiltrate: class II-positive monocytes/macrophages and T lymphocytes

In axonal forms (AMAN/AMSAN), antibodies (anti-GM1, anti-GD1a) directly attack axonal membranes at nodes of Ranvier.

Clinical Features

Cardinal features:

Symmetrical ascending weakness starting in the legs, progressing to arms and cranial muscles
Areflexia / hyporeflexia (invariable; may be absent early)
Mild sensory loss (vibration sense distally); sensory loss is NOT a prominent feature
Weakness may range from mild (can walk) to near-total quadriplegia

Cranial nerve involvement: 45-75% of cases

Bilateral facial paresis in ~50%
Extraocular and lower cranial nerve involvement less common

Autonomic dysfunction: ~65% of hospitalized patients

Orthostatic hypotension, hypertension, sinus tachycardia, urinary retention, ileus
Most significant in first 2-4 weeks

Respiratory failure: 9-30% require mechanical ventilation (increases with age)

Pain: Moderate to severe in ~70% during acute phase (extremities, back, interscapular area); may persist for a year in 1/3 of patients

Diagnosis

Required features (Asbury & Cornblath criteria):

Progressive weakness of both legs and arms
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:

CSF: Elevated protein with <10 cells/uL (cytoalbuminologic dissociation). Note: CSF may be normal in first 7-10 days and in up to 10% overall
Nerve conduction studies (NCS): Slowing/block in AIDP; reduced CMAP amplitudes in axonal forms
EMG: Helps exclude myopathy
Anti-GQ1b antibodies: >85% of Miller-Fisher syndrome

Differential Diagnosis

Warning signs suggesting an alternative diagnosis:

Warning Sign	Consider
Sensory-predominant	Sensory neuronopathy
Prominent bowel/bladder symptoms	Myelopathy
Spinal sensory level	Myelopathy
Persistently asymmetric weakness	Enteroviral myelitis, vasculitis, diabetic amyotrophy
Distal-predominant pattern	Toxic neuropathy (arsenic)
Slow progression (>4 weeks)	CIDP
CSF >50 WBCs/uL	HIV seroconversion, Lyme, CMV

Other key differentials: myasthenic crisis, botulism (unreactive pupils, no sensory symptoms), tick paralysis, transverse myelitis, critical illness polyneuropathy (normal CSF, axonal NCS pattern).

Treatment

Supportive Care (ICU monitoring is essential)

Respiratory monitoring: Intubate if vital capacity <1 L or NIF <-25 cmH2O (-70 cmH2O by some thresholds)
Monitor autonomic function and swallowing
DVT prophylaxis: subcutaneous heparin + compression devices
Prevent pressure ulcers, keratitis (facial diplegia), nosocomial infections
Nutritional support, physical therapy from early on

Disease-Modifying Therapy

Both options are equally effective; combination does not provide additional benefit:

1. IVIG (preferred in practice)

Dose: 2 g/kg divided over 2-5 days (adjust for cardiac/fluid status)
Should be started within 2 weeks of onset
Higher completion rate than PE, hence generally preferred
A second course of IVIG does NOT improve outcomes and should not be given
Mechanism: anti-idiotypic antibodies neutralize pathogenic autoantibodies

2. Plasma Exchange (PE)

4-5 exchanges (40-50 mL/kg each), alternate days
Using saline + albumin as replacement
Most beneficial within 2 weeks of onset; some benefit up to 30 days
4 exchanges optimal for moderate/severe cases; 6 exchanges show no additional benefit
Contraindications: active bleeding, severe cardiovascular instability, septicemia

Corticosteroids: NOT recommended as sole therapy; methylprednisolone + IVIG shows only slight initial advantage with no long-term benefit.

Prognosis

50% reach maximum disability within 2 weeks, 75% within 3 weeks, >90% within 4 weeks
Mortality: ~1-5% (modern era with ventilatory support; previously ~33%)
Most patients recover completely or with minor sequelae
~20% have persistent disability
Poor prognostic factors:
- Older age
- Preceding diarrheal illness (C. jejuni)
- Axonal variants (AMAN/AMSAN)
- Low CMAP amplitudes in upper extremities
- Greater severity of weakness at nadir

Sources: Bradley and Daroff's Neurology in Clinical Practice (Box 106.10-11, pp. 2663-2666); Goldman-Cecil Medicine (pp. 4080-4081)

Recent evidence note: A 2026 systematic review (PMID 41038424) examined exercise programs in GBS and CIDP for fatigue and functional capacity, consistent with current rehabilitation recommendations.

This is a shared conversation. Sign in to Orris to start your own chat.