Guillan-Barre Syndrome

Pathology

GBS is caused by an acute autoimmune inflammatory assault on peripheral nerves. The trigger for this autoimmune response is not fully understood. The mechanism is thought to involve molecular mimicry – i.e. exposure to pathogen-associated epitopes which resemble ganglioside epitopes present on peripheral nerve. In some cases there is a clearly-identifiable infectious trigger. Well-known triggers include:

  • C. jejuni
  • EBV
  • HIV
  • Zika

Guillan-Barre Syndrome is a group of several related disorders with slightly different pathology and clinical manifestations.

  • Acute inflammatory demyelinating polyradiculoneuropathy
  • Acute motor axonal neuropathy
  • Acute sensorimotor axonal neuropathy
  • Miller-Fisher syndrome
  • Bickerstaff’s brainstem encephalitis

Epidemiology

Incidence: 1 / 100,000 person-years

Risk factors:

  • Age
  • Male sex

Presentation

The classic presentation is of acute progressive, symmetrical, ascending weakness with areflexia, preceded by a non-specific viral illness in the preceding weeks. The symptoms worsen over days. Although sensory symptoms such as pain and paraesthesias are common, hard sensory signs are usually absent.

The weakness may involve:

  • The extra-ocular muscles
  • Bulbar muscles
  • The respiratory muscles

Other features

  • Autonomic neuropathy
    • GI: constipation, diarrhoea
    • Cardiovascular, tachy/bradyarrhythmias, hypo/hypertension
    • Horner’s syndrome
  • SIADH

GBS has a high mortality rate (5%). This is usually due to either:

  • Neuromuscular respiratory failure (type 2 respiratory failure), or
  • Autonomic instability: i.e. heart block, tachy/bradyarrhythmias

Time course:

  • Develops over days
  • Worst at 4 weeks

The various subtypes of GBS have different clinical and electrophysiological manifestations and are associated with different antibodies in serum.

Variant Clinical NCS Antibodies
AIDP Sensorimotor GBS

Cranial neuropathy

Autonomic dysfunction

Demyelinating polyneuropathy Variable
Acute motor axonal neuropathy (AMAN) Pure motor GBS

Cranial nerve involvement is very rare

Axonal polyneuropathy

Sensory APs normal

GM1a, GM1b
GD1a
GalNAc-GD1a
Acute motor sensory axonal neuropathy Mimics severe AMAN + sensory deficits Axonal polyneuropathy

Sensory APs absent/reduced

GM1

GD1a

Miller-Fischer syndrome Ataxia

Ophthalmoplegia

Areflexia

Mostly normal Gq1b
Pharyngeal-cervical-brachial variant Promiment weakness in oropharyngeal, facial, neck and shoulder muscles Mostly normal GT1a>GQ1b>>GD1a

 

Investigation

Diagnosis is based on a suggestive clinical picture supported by LP + electrophysiology. Serology for anti-ganglioside antibodies is not particularly helpful in making the diagnosis of most forms of GBS but does help to diagnose Miller-Fisher syndrome.

  • CSF analysis
    • Raised protein
    • Normal WCC
  • Nerve conduction studies
    • Axonal / demyelinating peripheral neuropathy (depends on subtype)

Differential diagnosis

GBS can be mimicked by acute disorders of:

  • The spinal cord
  • Peripheral nerve
  • The NMJ
  • Muscle

Causes of an acute polyneuropathy include:

  • Infective
    • Lyme
    • Tick paralysis
  • Neoplastic
    • Paraneoplastic
  • Vascular
    • Vasculitis
  • Inflammatory
    • Sarcoid
  • Toxic
    • Arsenic
    • Lead
    • Glue sniffing
  • Metabolic / Nutritional
    • Acute intermittent porphyria
    • B1 deficiency
    • Critical illness

Management

The goals of management are to prevent progression of the disease and monitor for complications.

Monitoring

The most feared complications of GBS are autonomic instability and neuromuscular respiratory failure. The two essential aspects of monitoring are therefore:

  • Forced Vital Capacity monitoring
  • Cardiac monitoring (HR & BP)

Ideally patients should be cared for in a high-depenency setting given the risk of acute deterioration.

Disease-modifying therapy

The options for definitive therapy are:

  • IVIG
  • Plasma exchange

Supportive care

  • Analgesia: neuropathic pain is common and can be treated with gabapentin or pregabalin.
  • VTE prophylaxis
  • NG tube if impaired swallowing
  • Monitor bowels (at risk of ileus)

Prognosis

80% recover within 6 months

15% have a more prolonged recovery

5% die

Poor prognostic factors:

  • Old age
  • Proximal weakness (predicts respiratory muscle involvement)
  • Rapid <7d onset
  • Requiring ventilation
  • Previos diarrhoeal illness with C. Jejuni
  • Small distal compound muscle action potentials