Author: Richard Loffhagen / Editor: Jason M Kendall / Reviewer: Kaja Rasheed, John Wilson / Codes: NeuC5, NeuP5, NeuP6, NeuP8, SLO1 / Published: 27/12/2021

Introduction

Context

Almost a century ago French neurologists Guillain and Barré gave their name to Guillain-Barré Syndrome (GBS), after they described the cases of two soldiers who presented with acute paralysis and areflexia, and later recovered. GBS is an acute immune mediated polyneuropathy with several variant forms

The incidence of the disease is static at 1–2/100,000.

It is more common in men (1.5:1) and with advancing age.

In spite of advances in the understanding of the pathogenesis and treatment options, it remains a severe disease, which can be difficult to diagnose and treat.

Pathophysiology and Variant Forms

The pathophysiology of GBS is thought to be an autoimmune response against peripheral nerve components namely the myelin sheath (causing AIDP) OR the axonal membranes (causing AMAN/ AMSAN)

The most common variant bilaterally affects motor and sensory nerves.

The key findings in GBS are profoundly-delayed conduction in nerve fibres, secondary to axonal demyelination. This occurs primarily in peripheral nerves and spinal roots, but may affect cranial nerves as well.

There is growing evidence that, at least in some cases, GBS is caused by an aberrant immune response to an infective trigger.

Subtypes

Subtypes include:

  • Acute inflammatory demyelinating polyneuropathy (AIDP). A subtype of GBS that has both sensory and motor symptoms. This is the most common form in the USA and western Europe
  • Acute motor axonal neuropathy (AMAN). This is a purely motor presentation, and more prevalent in children
  • Acute Sensorimotor Axonal Polyneuropathy (AMSAN).
  • Miller Fisher syndrome. This is a clinical variant of AIDP that is most commonly seen in the far east.

Clinical Assessment

Clinical Features

The diagnostic features of GBS are summarised below:

GBS characteristics

GBS is characterised by a rapidly-progressive, bilateral weakness, accompanied by reduced or absent tendon reflexes.

The symptoms and signs of GBS typically, but not invariably, move proximally.

Diagnostic features

  • Progressive weakness in both arms and legs, often starting with legs
  • Reduced, or absent, tendon reflexes
  • Relative symmetry of symptoms
  • Progression of symptoms up to four weeks
  • Followed by recovery in about 67% of patients
  • Absence of fever at presentation
  • Mild sensory symptoms or signs
  • Facial weakness or other cranial nerve involvement
  • Pain

Precipitants

The most common presentation is a post-infectious disorder in an otherwise healthy patient. Approximately two-thirds of patients report symptoms of an infection (gastrointestinal or upper respiratory) in the preceding three weeks.

Organisms implicated in preceding infections include:

Bacteria

  • Campylobacter jejuni
  • Haemophilus influenzae
  • Mycoplasma pneumoniae

Viruses

  • Cytomegalovirus
  • Epstein-Barr virus

Early symptoms

Early symptoms are pain, numbness, weakness or paraesthesia in the limbs, followed by a rapidly progressive symmetrical bilateral weakness.

This may extend to respiratory muscles or those innervated by cranial nerves.

Whilst the typical pattern of ascending weakness is well described, the weakness may affect arms and/or legs, and may take on a variety of patterns.

There are generally decreased or absent tendon reflexes in affected limbs.

Labratory findings

Albuminocytological dissociation on CSF analysis after a week of symptom onset is seen in about 66% of patients. This is characterised by raised Cerebrospinal fluid (CSF) protein (>0.4 g/L), with normal white cell count (WCC).

Progression of GBS

The weakness will reach its maximum within four weeks of onset and, in most cases, does so within two weeks.

There is normally a plateau period of varying length followed by a slow recovery phase of weeks, months or even years.

Disease progression beyond 8 weeks is classified as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Complications and Risk Stratification

Pain in GBS can be severe and resistant to treatment.

Autonomic failure occurs in up to two-thirds of patients, and can lead to cardiac arrhythmias and blood pressure fluctuations. This can occasionally be associated with sudden death.

Fatigue is a common and long-lasting complication.

Risk stratification

A largely arbitrary distinction is made between ‘mild’ and ‘severe’ GBS on the basis of whether the patient is able to walk.

The more severe the weakness, the worse the prognosis, and if respiratory muscles are affected then ICU treatment may be required.

Increasing age and a history of preceding diarrhoea are other factors indicating a poorer prognosis.

GBS is a progressive disease and all patients, whatever the severity, should be referred for in-patient specialist assessment and treatment.

Warning: Any patient in whom GBS is suspected must be admitted as progression of the disease can be rapid.

Differential Diagnosis

In countries where poliomyelitis has been eradicated, GBS remains the most common cause of acquired paralysis in children. For a classical presentation, making the diagnosis is relatively simple. However, presentation may be subtle and includes minor changes of gait or refusal to walk, associated with pain.

Learning Bite

The emergency physician needs to keep GBS in the differential diagnosis of the limping child.

Factors which make GBS a less likely diagnosis include a fever at presentation, raised cerebrospinal fluid white cell count (CSF WCC), an atypical presentation, or history of travel to developing countries (see Fig 1).

GBS Mimics

A comprehensive list of differential diagnoses which may mimic the neurological presentation of GBS is shown below.

Intracranial/spinal cord abnormalities

  • Brainstem encephalitis
  • Meningitis
  • Carcinomatosis/lymphomatosis
  • Transverse myelitis
  • Cord compression

Anterior horn cell abnormalities

  • Poliomyelitis
  • West Nile virus

Spinal nerve root abnormalities

  • Compression
  • Inflammation (e.g. cytomegalovirus)
  • Leptomeningeal malignancy

Peripheral nerve abnormalities

There are many causes of peripheral neuropathy:

  • Chronic inflammatory demyelinating polyneuropathy (CIDP)
  • Drug-induced neuropathy
  • Porphyria
  • Critical illness polyneuropathy
  • Vasculitis
  • Diphtheria
  • Vitamin B1 deficiency (Beriberi)
  • Heavy metal or drug intoxication
  • Tick paralysis
  • Metabolic disturbances (hypokalaemia, hypophosphataemia, hypermagnesaemia, hypoglycaemia)

Neuromuscular junction abnormalities

  • Myasthenia gravis
  • Botulism
  • Organophosphate poisoning

Muscular abnormalities

  • Critical illness polyneuromyopathy
  • Polymyositis
  • Dermatomyositis
  • Acute rhabdomyolysis

Investigation Strategies

The diagnosis of GBS is largely clinical, but the standard investigations are listed below.

The key diagnostic tests for the ED are the lumbar puncture, along with a screen of blood tests.

Lung function tests are vital for safe management of the patient.

Investigations

Acute investigations include:

  • Blood tests: FBC, ESR, U+E, LFT, CPK, CRP, glucose, Mg, calcium and phosphate
  • Stool culture (for C jejuni and others)
  • ECG
  • Lumbar puncture
  • Lung function tests if any respiratory compromise, or unable to walk

Other diagnostic tests include:

  • MRI may have a place in diagnosis. Selective anterior nerve root enhancement appears to be strongly suggestive of GBS. The cauda equina nerve roots are enhanced in 83% of patients
  • Nerve conduction and other electrodiagnostic studies may confirm and classify the diagnosis and is also used to prognosticate.
  • Immunological tests: Antibodies to GQ1B may confirm a Miller Fisher variant.
  • Nerve or muscle biopsy
  • Specific disease related tests e.g. HIV test

Interpretation of results

Learning Bite

A raised CSF protein (>0.4 g/L) with normal white cell count is the typical CSF finding in GBS.

However, CSF protein may be normal in the first week of the disease, but will have increased in more than 90% of cases by the end of the second week.

A raised serum CK suggests an alternative diagnosis such as a myositis.

Hypokalaemia and hypoglycaemia may also mimic GBS symptoms, and should be excluded.

Liver function tests are often mildly elevated in GBS.

Serial lung function tests are important as the onset of respiratory compromise can be rapid. Patients with an FVC less than 20mL/kg are candidates for prophylactic intubation and mechanical ventilation.

There is much current work regarding immunological studies in GBS. These may confirm an immune pathogenesis, and may affect long-term treatment in some cases, but currently have little place in the acute diagnosis, or treatment, of GBS.

Management

Initial Treatment

Initial treatment is supportive. Plasma exchange (PE) or intravenous immunoglobulins (IVIG) are indicated in the treatment of GBS patients who are severely affected (unable to walk). Corticosteroids are of no proven benefit.

Patients should have regular monitoring of lung function – the more severely affected will require respiratory support and must be managed in the intensive care unit (ICU).

The effect of GBS on autonomic function should not be forgotten, and initially continuous cardiac monitoring and regular blood pressure readings should be taken.

Specific scenarios are explained below.

Severely affected patients (unable to walk)

PE or IVIG should be initiated for more severely affected patients, ideally within the first two weeks of symptoms.

A Cochrane review did not find either treatment better than the other, nor was the combination of both treatments superior to either treatment alone.

No benefit has been demonstrated in the use of oral corticosteroids. Trials of intravenous corticosteroids have shown some benefit but this has not reached statistical significance.

Mildly affected patients (able to walk)

Although there is some evidence that treatment with PE may be beneficial, there are no adequate trials to support the use of IVIG or PE in GBS patients who retain the ability to walk.

Miller Fisher syndrome (MFS)

The final outcome of MFS is generally good.

There are no randomised controlled trials of IVIG or PE usage, and what trials there are show little benefit.

Treatment Options

The treatment options for GBS are detailed below.

Monitoring
  • Lung function initially every four hours
  • ECG
  • BP
  • Autonomic function – pupils and ileus
  • Check for swallowing dysfunction
General measures
  • Pain relief: try to avoid opioids
  • Chronic neuropathic pain: amitriptyline or antiepileptic drugs
  • DVT prophylaxis
  • Eye care
  • Meticulous nursing to avoid pressure sores
  • Physiotherapy to avoid contractures
  • Consider early ICU admission for severely affected patients
Indications for ICU admission
  • Risk of aspiration pneumonia
  • Requiring ventilated support
  • Rapidly-progressive disease
  • Labile heart rate or blood pressure
Specific treatments
  • IVIG or PE for those unable to walk, ideally to start within two weeks of onset of symptoms
  • Typical IVIG regimen: 0.4g/kg for five days
  • Typical PE regimen: total exchange of five plasma volumes in two weeks
  • Retreatment with IVIG may be indicated if there is a secondary deterioration

Prognosis and Followup Strategies

Approximately one quarter of severely-affected patients require ventilatory support.

Even with IVIG or PE, one fifth of those severely affected remain unable to walk at six months.

Prognosis can be predicted from the acute stage of the disease, based on:

  • Increasing patient age
  • Severity of disability
  • History of preceding diarrhoea

These are all poor prognostic factors.

Learning bite

GBS is fatal in 3-10% of cases. The cause of death is multifactorial.

Key Learning Points

Key Learning Points

  • GBS is a range of diseases affecting both the axon and myelin sheath
  • Post infectious presentation is common especially Campylobacter Jejuni diarrhoea
  • Typical ascending symmetrical paralysis is common, with absent reflexes
  • Presentation may be subtle with pain or minor gait changes a common feature GBS should be in the differential for the limping child
  • Raised CSF WCC, fever at presentation, atypical presentation or history of foreign travel suggest alternative diagnoses
  • All cases should be referred for admission
  • ICU care is required for those with significant respiratory problems
  • ECG and BP monitoring are required
  • Severe cases should be treated with IVIG
  • Corticosteroids are of no proven benefit
  • Prognosis in children is very good

References

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