Guillain-Barré Syndrome

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Introduction

Guillain-Barré Syndrome (GBS) is an acute, inflammatory neuropathy, primarily affecting the peripheral nervous system.1 It is a relatively rare condition, with an incidence of approximately 2/100,000 every year in the UK. This number, however, increases with age and is more prevalent in men than women.2

While the full aetiology of Guillain-Barré Syndrome is not fully understood, two-thirds of patients who develop GBS have a recent history of either an upper respiratory tract infection or gastroenteritis.

Established pharmacological therapies for GBS have shown improved patient outcomes, but management focuses on reducing the risk of respiratory compromise, which is the major risk with GBS. Respiratory compromise occurs in approximately 20-30% of GBS patients.1

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Aetiology

Around 66% of GBS cases involve a previous history of either an upper respiratory tract infection (URTI) or a gastrointestinal infection.1 The most commonly-associated organisms are cytomegalovirus, Epstein-Barr virus, Mycoplasma, and Campylobacter jejuni.3

Guillain-Barré Syndrome is considered to be an autoimmune condition. Current evidence suggests GBS occurs due to immune system activation against these pathogens, where the immune response mistakes key components of peripheral nerves for the virus it is attacking. This phenomenon is termed molecular mimicry.3 

The result is demyelination of both motor and sensory peripheral nerves, impacting their ability to relay information between the central nervous system and the periphery. This causes clinical features such as paraesthesia and weakness.

There have been reports of patients developing GBS following Zika virus outbreaks or more rarely COVID-19.3

Pathophysiology

There are four subtypes of GBS:2

  • Acute inflammatory demyelinating polyneuropathy (AIDP): the most common variant of GBS in Western Europe and North America, primarily affecting the myelin sheath of affected nerves.
  • Acute motor axonal neuropathy (AMAN): a form of GBS more common in Asian countries that primarily damages the axons of motor neurons specifically. This results in a purely motor presentation, as opposed to the more common sensorimotor neuropathy in AIDP.
  • Acute motor sensory axonal neuropathy (AMSAN): affecting axons of both motor and sensory neurons. This variant is associated with a poorer rate of recovery.
  • Miller-Fisher syndrome: a form of GBS defined by antibodies to the GQIb ganglioside, typically associated with a triad of ophthalmoplegia, ataxia, and areflexia. No treatment is required for Miller-Fisher Syndrome.

A patient with GBS may exhibit characteristics of one or more variants. Identifying the subtype of GBS is important as they vary as to the degree of respiratory involvement, and therefore the indication for early pharmacological therapies or intensive care unit admission.

Patterns of symptom distribution of different variants of Guillain-Barre Syndrome
Figure 1. Patterns of symptom distribution of different variants of Guillain-Barre Syndrome

Clinical features

History

GBS can present at any age, however, is more common in older men. A typical history may include recent viral infection or travel abroad (with increased risk of Campylobacter infection), and the first neurological signs manifesting around 2-4 weeks post-infection.2

Typical symptoms of GBS include:3

  • Rapidly progressive symmetrical weakness typically in an ascending pattern: beginning in the lower limbs and hands and starting to affect arms, trunk, facial muscles, and possibly respiratory muscles as time progresses
  • Paraesthesia (numbness and tingling) in the lower limbs and hands
  • Issues with balance or coordination, especially in the lower body
  • Back or limb pain which can be worse at night
  • Difficulties with vision, as cranial nerves affected
  • Difficulties with speech, swallowing or chewing
  • Autonomic dysfunction, including palpitations, heart failure, bowel and bladder issues

There is variation in the progression of symptoms and can take hours, days, or weeks to resolve. Symptoms will progress up to a maximum of 4 weeks, after which two-thirds of patients will recover and regain normal function within 6-12 months.2

Clinical examination

A thorough neurological examination (including upper limbs, lower limbs and cranial nerves) should be carried out on all patients suspected of Guillain-Barré Syndrome.

Typical clinical findings on neurological examination include:4

  • Symmetrical bilateral weakness ascending from the lower limbs first up to arms, trunk, bulbar, and ocular muscles
  • Reduced sensation over areas of weakness (such as legs and hands)
  • Areflexia: absent or reduced reflexes
  • Autonomic dysfunction: heart arrhythmias, tachycardia, hyper- or hypotension, anhidrosis, respiratory dysfunction

Differential diagnoses

Differential diagnoses to consider which also cause acute, potentially progressive paralysis include:4

  • Stroke
  • Encephalitis
  • Myasthenia gravis
  • Polymyositis
  • Myelopathy
  • Botulism

Investigations

Guillain-Barré Syndrome is a clinical diagnosis. However, investigations help stratify risk in patients. Due to the rare and complex nature of GBS, all suspected cases should be referred to hospital for specialist review and possible admission.

Bedside investigations

Relevant bedside investigations include:4

  • Serial lung function tests: the greatest risk in a patient with GBS is the threat of respiratory compromise, as more muscles are at risk of paralysis as the condition progresses. Patients should have regular and frequent measurements of their Forced Vital Capacity (FVC). Any patients with an FVC <50% predicted or with rapid deterioration should be reviewed for intubation and mechanical ventilation.
  • Electrocardiogram (ECG): to screen for possible heart arrhythmias and heart block
  • Continuous BP monitoring (in severe cases): GBS can cause autonomic dysfunction. Continuous monitoring would often take place in an ICU environment.
Handheld spirometry device
Figure 2. Handheld spirometry device

Laboratory investigations

Relevant laboratory investigations include:2

  • Full blood count: for baseline
  • Urea and electrolytes: up to 50% of patients may have syndrome inappropriate ADH secretion (SIADH), the mechanism is unclear, but this may be a side effect of IVIg, one of the therapies for GBS. Hypokalemia can also mimic GBS symptoms and should be excluded.
  • Liver function tests: often associated with mildly raised ALT and AST
  • Glucose: hypoglycemia can mimic GBS symptoms
  • Creatine kinase (CK): to exclude a polymyositis

Other specialist immunological blood tests may be performed, specifically for Anti-GQIB, which is more specific for Miller-Fisher syndrome.

Imaging

There are no definitive imaging investigations for GBS. An MRI spine may be performed to rule out myelopathy. Some specialists may request ultrasound imaging of peripheral nerves.

Special tests

Other relevant investigations include:5

  • Nerve conduction studies: shows the rate at which electrical signals travel across the nerves. In GBS, due to the diffuse polyneuropathy affecting both sensory and motor neurons, this test often shows a much slower signal rate than normal (though it may be normal in early disease). This is considered the gold standard investigation if there is diagnostic uncertainty.
  • Lumbar puncture: often shows CSF containing increased protein and normal cell count. This is usually not seen in the first week of the illness but becomes more evident as it progresses further.

Management

In the acute phase of Guillain-Barré Syndrome, there is a risk of rapid deterioration. As such, all patients should be admitted for assessment and close monitoring. 

General management

General management of GBS includes:2

  • Serial lung function tests (FVC): every four hours to screen for respiratory compromise
  • Supportive treatment: intravenous fluids, heart rate control (usually sufficient for mild-to-moderate cases)
  • Venous thromboembolism (VTE) prophylaxis
  • Eye care
  • Pressure sore screening and management
  • Pain relief: neuropathic pain medications such as amitriptyline or gabapentin. May require opiates for severe pain.
  • Physiotherapy: to help regain motor function and avoid contractures
  • Swallow assessment: patients may require nasogastric feeding if dysphagia is present

Corticosteroids, often used for other classical autoimmune conditions, have shown no clinical benefit in GBS.

Further management

There are two current therapies designed to minimise the autoimmune damage being done to the nerves:5

  • Plasma exchange: involves plasma within the blood being removed, filtered to remove autoantibodies, and returned to circulation around the body. This decreases the severity of GBS by removing the autoantibodies within the blood damaging the nerves.
  • IV immunoglobulin therapy (IVIg): an infusion of donor immunoglobulins (antibodies) which dilutes the ability of the autoantibodies to inflict damage upon the body. This therapy has proven effective in reducing recovery time.

Both of these therapies show improved clinical outcomes for patients when started within two weeks of symptom onset. Almost all patients admitted with Guillain-Barre syndrome (apart from those with Miller-Fisher syndrome) will be treated with plasma exchange or intravenous immunoglobulin.

Admission to intensive care

Indications for intensive care unit admission in severe GBS include:4

  • Requirement of significant respiratory support (mechanical ventilation)
  • Rapidly-progressing muscle weakness
  • Rapidly fluctuating blood pressure or cardiac arrhythmias
  • Swallow dysfunction, with the risk of aspiration pneumonia

The Erasmus GBS Respiratory Insufficiency Score (EGRIS) can help predict the risk of respiratory compromise in the first week of admission and guide decision-making regarding intensive care unit admission.6


Complications

Complications of Guillain-Barré syndrome may include:4

  • Respiratory compromise (the leading cause of death in GBS patients)
  • Venous thromboembolism
  • Infection
  • Aspiration pneumonia
  • Cardiac arrhythmias
  • Ileus
  • Long-term disability, requiring a wheelchair or walking aid
  • Persistent neuropathic pain or fatigue
  • Psychological trauma of experience causing lasting disability and distress

The general prognosis is good with 80% of patients regaining the ability to walk six months following the course of the disease. However, 20% of patients have persistent neurological dysfunction. There is a mortality rate of 3-10%.4


Key points

  • Guillain-Barre Syndrome is an acute, diffuse polyneuropathy typically affecting the lower limbs first and progressing to the arms, trunk, face
  • While the specific cause is not entirely known, it often occurs 2-3 weeks after a viral infection (respiratory or gastrointestinal)
  • The most common symptoms include ascending paraesthesia and muscle weakness first affecting the legs and arms and then moving onto the rest of the body. This can cause respiratory compromise (the most serious complication of GBS).
  • The diagnosis of GBS is clinical but can be aided by nerve conduction studies and lumbar puncture
  • Patients with GBS require constant monitoring of vitals, including pulmonary function tests, blood pressure, and heart rate
  • Management includes VTE prophylaxis, eye and pressure sore care, supportive treatments, and long-term physiotherapy. More targeted treatments including plasma exchange or IVIg can be considered in severe cases.
  • There is a low threshold for ICU admission in patients at high risk of respiratory compromise, rapidly progressing disease or aspiration pneumonia.

Reviewer

Dr James Miller

Consultant Neurologist

Royal Victoria Infirmary, Newcastle


Editor

Dr Chris Jefferies


References

  1. BMJ Best Medical Practice. Guillain-Barre Syndrome. Last reviewed 19 Aug 2022. Available from: [LINK]
  2. Loffghan, R. Royal College of Emergency Medicine Learning. Guillain-Barre Syndrome. Published 27 Dec 2021. Available from: [LINK]
  3. National Institute of Neurological Disorders and Stroke. Guillain-Barré Syndrome Fact Sheet. Published June 2018. Available from: [LINK]
  4. Shaf, Suchita. Patient UK. Guillain-Barre Syndrome. Last edited 14 July 2022. Available from: [LINK]
  5. National Organization for Rare Diseases. Guillain-Barre Syndrome. Published 2020. Available from: [LINK]
  6. Walgaard, C., Lingsma, H.F., et al. Annals of Neurology 2010. Prediction of respiratory insufficiency in Guillain-Barré syndrome, Published 25 May 2010. Available from: [LINK]

Image References

  • Figure 1. Leonhard, S.E., Mandarakas, M.R., Gondim, F.A.A. et al. Symptom distribution of different variants of Guillain-Barre Syndrome. License: [CC BY 4.0]
  • Figure 2. Cosmed. Desktop spirometer (cropped). License: [CC BY-SA 3.0]

 

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