Guillain-Barré syndrome is an acute, inflammatory, immune-mediated polyradiculoneuropathy characterised by rapidly progressive, symmetrical muscle weakness and diminished or absent deep tendon reflexes 1,2. It is often triggered by a preceding infection and can lead to significant morbidity, including respiratory failure and paralysis, necessitating intensive care 1,2. The syndrome was first described by Guillain, Barré, and Strohl in 1916 2. It represents a neurological emergency requiring prompt diagnosis and management.
Epidemiology
The incidence of GBS is estimated at approximately 1 to 2 cases per 100,000 person-years, with a lifetime risk of about 1 in 1000 1. Incidence increases with age, particularly after 50 years, and there is a slight male predominance 1. Seasonal variations may occur, with peaks often observed during winter and spring months in temperate climates 1.
Aetiology
secondary associations: While infection is the most common trigger, GBS can occasionally be associated with other conditions such as surgery, trauma, malignancy, or certain systemic diseases, although these are less frequent 1.
primary causes / triggers: GBS is typically post-infectious, most commonly triggered by bacterial infections, particularly Campylobacter jejuni gastroenteritis (responsible for up to 30% of cases) 1,2. Other implicated infections include cytomegalovirus (CMV), Epstein-Barr virus (EBV), Mycoplasma pneumoniae, influenza virus, and Zika virus. In some cases, vaccination (e.g., adenovirus vector vaccines) has been associated with GBS, although the risk is very low 1.
Pathophysiology
GBS is an autoimmune disorder where the immune system mistakenly attacks components of the peripheral nervous system, leading to inflammation and demyelination or axonal damage 1,2. The main pathological subtypes are acute inflammatory demyelinating polyradiculoneuropathy (AIDP), the most common form in Western countries, characterised by primary demyelination of peripheral nerves and nerve roots; acute motor axonal neuropathy (AMAN), primarily affecting motor axons; acute motor and sensory axonal neuropathy (AMSAN), affecting both motor and sensory axons; and the Miller Fisher syndrome (MFS), typically associated with anti-GQ1b antibodies and characterised by ophthalmoplegia, ataxia, and areflexia 1,2,3. The underlying mechanism involves molecular mimicry, where antibodies generated against infectious agents cross-react with peripheral nerve components 1.
Clinical presentation
physical examination signs: Hallmark signs include progressive, symmetrical weakness (often more proximal than distal), hyporeflexia or areflexia (loss of deep tendon reflexes), and relative preservation of sensation, although sensory symptoms like paresthesias are common 1. Cranial nerve palsies, particularly facial nerve (VII) and oculomotor nerves (III, IV, VI), are frequent. Respiratory muscle weakness is a serious complication and requires close monitoring 1.
presenting symptoms: The classic presentation involves rapidly progressive, ascending, symmetrical muscle weakness, typically starting in the lower limbs and spreading upwards over days to weeks 1. Patients often experience paresthesias (tingling or numbness) in the hands and feet preceding weakness. Autonomic dysfunction (e.g., fluctuations in blood pressure, heart rate abnormalities, urinary retention) and cranial nerve involvement (e.g., facial weakness, diplopia, dysphagia) can also occur 1.
Investigations
Bedside & Laboratory
specific test name: Cerebrospinal fluid (CSF) analysis is crucial. Typically, CSF shows albuminocytologic dissociation: elevated protein levels (usually >0.55 g/L) with a normal or only mildly elevated white blood cell count (<10 cells/µL) 1. This finding may not be present in the first week of illness but usually develops within 1-2 weeks. Nerve conduction studies (NCS) and electromyography (EMG) can help confirm the diagnosis, differentiate subtypes (demyelinating vs. axonal), and assess severity, showing slowed conduction velocities and conduction block in AIDP, or reduced amplitudes in axonal variants 1.
Imaging & Special Investigations
specific modality / diagnostic study: Neuroimaging (MRI of the spine) is generally not required for diagnosis but may be used to exclude other conditions like spinal cord compression. It may show enhancement of nerve roots in GBS 1.
Management
definitive / long-term management: There is no specific cure for GBS. Management focuses on supportive care and rehabilitation. Most patients recover fully or with residual mild deficits over weeks to months, although some may experience persistent weakness, sensory disturbances, or fatigue 1. Long-term rehabilitation, including physiotherapy and occupational therapy, is essential to optimise functional recovery 1.
acute / first-line management: Management focuses on supportive care, including close monitoring of respiratory function (vital capacity, negative inspiratory force), cardiovascular stability (blood pressure, heart rate), and prevention of complications (deep vein thrombosis, pressure sores) 1. Patients with significant weakness or respiratory compromise require admission to a high-dependency unit or intensive care unit. Immunomodulatory therapy with either plasma exchange (plasmapheresis) or intravenous immunoglobulin (IVIg) is indicated for patients unable to walk unaided or those requiring mechanical ventilation, ideally initiated within 2-4 weeks of symptom onset 1. NICE guidelines recommend either treatment, with plasma exchange typically involving 5 sessions over 7-14 days 1.
Differential diagnosis
Myasthenia gravis: Characterised by fluctuating muscle weakness that worsens with activity and improves with rest, often affecting ocular, bulbar, and limb muscles. Reflexes are typically preserved. Diagnosis involves acetylcholine receptor antibody testing and electrophysiological studies (repetitive nerve stimulation, single-fibre EMG).
Tick paralysis: Caused by neurotoxin from certain ticks. Presents with rapidly ascending paralysis similar to GBS, but often with a history of tick bite and absence of CSF protein elevation. Removal of the tick leads to rapid improvement.
Transverse myelitis: Typically presents with more rapid onset, distinct sensory level, bowel/bladder dysfunction, and upper motor neuron signs (spasticity, hyperreflexia) rather than the areflexia seen in GBS. CSF may show pleocytosis.
Prognosis & complications
The prognosis for GBS is generally good, with most patients making a significant recovery, although complete recovery can take months to years 1. Mortality is around 5%, usually due to respiratory failure, autonomic instability, or complications like pulmonary embolism or infection 1. Major complications include respiratory failure (requiring mechanical ventilation in 25-30% of patients), autonomic dysfunction (cardiac arrhythmias, blood pressure instability), deep vein thrombosis, pressure sores, and persistent neurological deficits 1.
