Overview

Guillain-Barré Syndrome (GBS) is an acute, immune-mediated polyneuropathy typically triggered by a preceding gastrointestinal or respiratory infection. It is characterised by an autoimmune attack on the peripheral nerves, leading to mainly demyelination but also axonal degeneration, which impairs nerve conduction and causes muscle weakness and paralysis. GBS affects about 1–2 per 100,000 people annually. People of all ages can be affected, but it is more common in adults and in males.

Aetiology and Risk Factors

GBS is a post-infectious acute auto-immune mediated neuropathy that is typically preceded by a gastrointestinal or respiratory tract infection with the most common pathogens including:

• Campylobacter Jejuni (seen in 20-35% of cases)
• Cytomegalovirus (CMV)
• Epstein-Barr virus
• Mycoplasma Pneumoniae

Pathophysiology

GBS is often preceded by a gastrointestinal or URT infection which triggers an autoimmune response against nerve sheath and axons. The main mechanism is thought to be through molecular mimicry, whereby the most common organism C. jejuni has surface antigens that resemble gangliosides on peripheral nerves. As a result, the body creates ganglioside autoantibodies, of which exist multiple variants, that attack components of the myelin sheath or axons of peripheral nerves. 

In the most common variant, acute inflammatory demyelinating neuropathy (AIDP), immune cell infiltration and macrophage-mediated stripping of the myelin sheath causes segmental demyelination, resulting in poor nerve conduction (conduction block) and subsequent muscle weakness and flaccid paralysis. In this variant however there is potential for full recovery. In the acute motor axonal neuropathy (AMAN) variant (more common in C. Jejuni infections), the immune attack is centred at the nodes of Ranvier, resulting in direct axonal degeneration. AMAN has a more severe and prolonged recovery time.^{1, 2, 3, 4}

Clinical Manifestations 

GBS typically presents as progressive, symmetrical, ascending muscle weakness that reaches nadir by about the 4^th week of infection. Patients commonly experience flaccid paralysis, varying ranges of areflexia or hyporeflexia and a distal-proximal progression of weakness. It often causes sensory changes in the hands followed by the feet. Cranial nerve involvement involves the facial and bulbar muscles leading to dysphagia and facial muscle weakness.  Patients are also likely to experience neuropathic pain.

Up to two thirds of patients experience autonomic involvement which can manifest In the form of cardiac arrhythmias, hyper/hypotension ileus and urinary incontinence. Respiratory muscle weakness is seen in 25% of cases and has resulted in some population groups requiring mechanical ventilation.^{1, 5, 6, 7}

Miller Fisher syndrome is a rare variant of GBS characterised by a distinct triad of:

• Ophthalmoplegia (paralysis of eye movements)
• Ataxia (gait and limb incoordination)
• Areflexia (absent reflexes)

Diagnosis 

GBS is considered to be a clinical diagnosis that can be made on bedside if suspicion is high.  Further investigations can be done to rule out differentials and determine the variant of GBS, but no investigation is specific in the diagnosis.^{1, 7, 8}

• Cerebrospinal fluid testing: Raised CSF proteins but may be normal in the first week of infection. WCC is usually normal in most cases
  • Raised CSF proteins with normal WCC is termed albuminocytologic dissociation
• Nerve conduction studies: Can help distinguish between demyelination and axonal disease
  • Findings may include: Conduction blocks, prolonged or absent “F” waves 
• Anti-ganglioside antibodies
  • Anti-GM1: worse prognosis
  • Anti-GD3 
  • Anti-GQ1b: associated with Miller Fisher syndrome
  • Has a smaller diagnostic role but may have a prognostic role
• Other blood tests to exclude conditions that mimic GBS such as electrolyte deficiencies, porphyria and IgA deficiency

Differential Diagnosis

• Myasthenia Gravis – Fluctuating proximal and ocular weakness, normal reflexes and sensation, no autonomic symptoms.
• Botulism – Descending paralysis with early cranial nerve involvement, dilated pupils, autonomic dysfunction, preserved sensation.
• Tick Paralysis – Rapid ascending flaccid paralysis, preserved sensation, dilated pupils, improves after tick removal.
• Transverse Myelitis – Weakness with sensory level, early bladder/bowel dysfunction, back pain, asymmetric signs, MRI shows spinal cord lesion.
• Acute Intermittent Porphyria – Motor neuropathy with abdominal pain, autonomic features (e.g. tachycardia), dark urine, precipitated by drugs or stress.

Treatment

Overall, the management of GBS involves disease modifying therapies and general supportive treatment^{1, 8}

• Disease-modifying treatment:
  • IV immunoglobulin (IVIg): 2 g/kg over 5 days
    • Has an immune modulating effect
    • Treatment of choice for most GBS cases
  • Plasma Exchange (PE)
    • Must be started as early as possible
    • If started early, as effective as IVIg
  • If patients show no response to treatment after 2 weeks, consider repeat courses 
  • Note there is no added benefit of combination IVIg and PE
• General supportive management:
  • Respiratory support:
    • Monitor vital capacity regularly (failure to recognise respiratory issues is fatal)
  •  Swallowing assessments
  • Cardiac:
    • ECG and BP monitoring
  • Neuropathic pain:
    • Treatment with gabapentin, carbamazepine or analgesics like tramadol
  • Physiotherapy:
    • Begin early rehabilitation to prevent contractures and aid recovery

Indications for intensive care unit (ICU) ⁵

• evolving respiratory distress with imminent respiratory insufficiency (drop in arterial O2, pulse oximetry or reduced vital capacity)
• severe autonomic cardiovascular dysfunction (for example, arrhythmias or marked variation in blood pressure)
• severe swallowing dysfunction 
• diminished cough reflex
• rapid progression of weakness

Complications and Prognosis

• Clinical improvement is usually most extensive in the first year after disease onset and can continue for >5 years.
• GBS typically has a good prognosis, with 80% of patients achieving full recovery within 6 months. 
• 5% mortality rate in the acute phase (typically with autonomic involvement)
• 20% of patients may have a long term disability and lose the ability to walk without aids
• GBS is typically a monophasic illness, though a subset of patients may experience deterioration after initial stabilisation or improvement with treatment — a pattern known as treatment-related fluctuation (TRF). 
• True relapses of GBS occur in approximately 2–5% of cases
• Complications include:
  • Respiratory failure (requiring ventilation)
  • Bulbar palsy (risk of aspiration, swallowing difficulties)
  • Autonomic dysfunction (cardiac arrhythmias, BP instability)

References

1. National Institute of Neurological Disorders and Stroke. Guillain-Barré Syndrome [Internet]. Bethesda (MD): National Center for Biotechnology Information; 2018 [cited 2025 Jun 29]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532254/
2. Ropper AH, Samuels MA, Klein JP. Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis [Internet]. UpToDate; [cited 2025 Jun 29]. Available from: https://www.uptodate.com/contents/guillain-barre-syndrome-in-adults-pathogenesis-clinical-features-and-diagnosis
3. Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med. 2012;366(24):2294–2304. doi:10.1056/NEJMra1114525
4. Brown WF, Feasby TE. Conduction block and denervation in Guillain-Barré polyneuropathy. Brain. 1984;107(Pt 1):219–239. doi:10.1093/brain/107.1.219
5. Leonhard SE, Mandarakas MR, Gondim FAA, et al. Diagnosis and management of Guillain-Barré syndrome in ten steps. Nat Rev Neurol. 2019;15(11):671–683. doi:10.1038/s41582-019-0250-9
6. Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet. 2016;388(10045):717–727. doi:10.1016/S0140-6736(16)00339-1
7. BMJ Best Practice. Guillain-Barré syndrome: Diagnosis approach [Internet]. BMJ Publishing Group; [cited 2025 Jun 29]. Available from: https://bestpractice.bmj.com/topics/en-gb/176/diagnosis-approach
8. Turner MR, Talbot K. Oxford Handbook of Neurology. 2nd ed. Oxford: Oxford University Press; 2014.