Guillain-Barré syndrome

Synonym: acute inflammatory polyneuritis

What is Guillain-Barré syndrome?

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy characterised by weakness, paraesthesiae and hyporeflexia. It is a rare but potentially fatal autoimmune disorder that causes axonal degeneration and demyelination of peripheral nerves and nerve roots.

About 75% of patients have a history of preceding viral or bacterial infection, usually of the respiratory and gastrointestinal tract. Several infections have been linked to GBS, including Campylobacter jejuni, Epstein Barr virus, hepatitis E virus, influenza, cytomegalovirus, mycoplasma, human immunodeficiency virus, and Zika virus.¹ There may also be a link to SARS-CoV-2.² This association with preceding infection suggests that antibodies to the infectious organism also attack antigens in peripheral nerve tissue, through molecular mimicry.

The closest association between antibodies and the neurological disease is seen with the closely related Miller Fisher syndrome (also called Fisher's syndrome), where more than 90% of patients have antibodies against the ganglioside GQ1b. Miller Fisher syndrome is thought to be an inflammatory neuropathy affecting the cranial nerves (especially the eye muscles, causing ophthalmoplegia), accompanied by areflexia and ataxia but not weakness.

Bickerstaff's brainstem encephalitis is considered part of Miller Fisher syndrome with additional features of drowsiness and extensor plantar responses. Some cases of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) have features of the Miller Fisher syndrome but with associated weakness.³

Gullain-Barré syndrome consists of a number of subtypes, including:⁴

• AIDP.

• Acute motor and sensory axonal neuropathy (AMSAN): associated with the antibodies GM1, GM1b and GD1a.

• Acute motor axonal neuropathy (AMAN): associated with the antibodies GM1, GM1b, GD1a and GalNac-GD1a.

• Acute sensory neuronopathy: associated with GD1b antibodies.

• Acute pandysautonomia.

About 95% of cases of Guillain-Barré syndrome are AIDP.

How common is Guillain-Barré syndrome?(Epidemiology)⁵

• The crude incidence of typical Guillain-Barré syndrome in North America and Europe is 0.8-1.9 per 100,000 person-years.

• The incidence increases by 20% for every 10-year increase in age.

• There is an increased incidence in males compared to females.

• Peak ages are 15-35 years and 50-75 years.

Risk factors

• History of acute viral or bacterial infectious illness from 1-3 weeks prior to the onset of weakness.

• Vaccinations: live and dead vaccines have been implicated. Although there have been case reports of GBS following COVID-19 vaccination, a causal link has not yet been established.⁶

• Malignancies - eg, lymphomas, especially Hodgkin's disease.

• Pregnancy: incidence decreases during pregnancy but increases in the months after delivery.

• Other: surgery, trauma, or bone marrow transplantation.⁷

Guillain-Barré syndrome symptoms and signs⁸

History

• Weakness:
  

  • In up to 76% of cases, onset occurs approximately three weeks after an infectious illness.

  • Onset is acute and the subsequent time course is monophasic.

  • The pattern is usually an ascending, progressive, symmetrical flaccid weakness, starting in the legs and/or arms.

  • This reaches a level of maximum severity at around 2-4 weeks after initial onset, followed by a plateau phase (where symptoms remain persistent and unchanged) of variable duration, before recovery begins.

  • Facial weakness, dysphasia or dysarthria may develop.

  • In severe cases, muscle weakness may lead to respiratory failure.

• Pain: neuropathic pain may develop, particularly in the legs. Back pain may be another feature.

• Reflexes: these may be reduced or absent.

• Sensory symptoms: these can include paraesthesiae and sensory loss, starting in the lower extremities.

• Autonomic symptoms: involvement of the autonomic system may present with reduced sweating, reduced heat tolerance, paralytic ileus or urinary hesitancy. Severe autonomic dysfunction may occur.

Examination

The following features may be present:

• Hypotonia.

• Demonstrable altered sensation or numbness.

• Reduced or absent reflexes.

• Fasciculation may occasionally be noted.

• Facial weakness - may be asymmetrical.

• Autonomic dysfunction - fluctuations of heart rate and arrhythmias, labile blood pressure and variable temperature.

• Respiratory muscle paralysis.

Differential diagnosis

Other causes of acute paralysis include:

• Brain: stroke, brainstem compression, encephalitis.

• Spinal cord: cord compression, poliomyelitis, transverse myelitis.

• Anterior horn cell: poliovirus or enterovirus infection

• Nerve root: CMV and HIV radiculitis

• Peripheral nerve: vasculitis, lead poisoning, porphyria,Lyme disease, thiamine deficiency, diphtheria.

• Neuromuscular junction: myasthenia gravis, botulism,Lambert-Eaton syndrome.

• Muscle: hypokalaemia, polymyositis.

Investigations

Diagnosis is usually made on clinical grounds. Diagnostic criteria exist, such as the the US National Institute of Neurological Disorders and Stroke (NINDS) and the Brighton Collaboration Guillain-Barré Syndrome Working Group criteria, but they do not cover all subtypes or presentation of GBS, which can be variable in its presentation. The following investigations may be helpful:

• Nerve conduction studies: are the most useful test to support the diagnosis of GBS. Although they can be normal in the early stages of the disease, in most patients with GBS they will be abnormal. If studies are initially normal, it is recommended that they be repeated after two weeks.⁹

• Lumbar puncture: most patients have an elevated level of cerebrospinal fluid (CSF) protein, with no elevation in CSF cell counts. The rise in the CSF protein may not be seen until 1-2 weeks after the onset of weakness.

• Spirometry: forced vital capacity is a major determinant of the need for admission to ICU and then the need for intubation.

• Blood tests: FBC, LFTs, glucose and renal function. These usually help rule out other causes of acute flaccid paralysis, but hepatic aminotransferases may be very high in GBS, and liver dysfunction is associated with more severe disease.¹⁰

• Electrolytes: inappropriate antidiuretic hormone secretion occurs in some patients; serum and urine osmolarity studies are indicated if it is suspected.³

• ECG: many different abnormalities may be seen - eg, second-degree and third-degree AV block, T-wave abnormalities, ST depression, QRS widening and a variety of rhythm disturbances.

• Antibody screen: antibodies to peripheral and central nerves may be present.

• Other: these include viral or bacterial serology and neuroimaging, and tests to rule out other causes, as appropriate. Ultrasound imaging of peripheral nerves is an emerging option.

Guillain-Barré syndrome treatment and management

Management in the acute phase of GBS involves a combination of supportive care, disease-modifying therapy in the form of plasma exchange or intravenous immunoglobulin (IVIG), and preventing and managing complications.

• Plasma exchange:¹¹
  

  • A Cochrane review found significantly greater improvement with plasma exchange than supportive care alone, without a significant increase in serious adverse events.

  • There was a small but significant increase in the risk of relapse during the first 6-12 months after onset in people treated with plasma exchange.

  • However, after one year, full recovery was significantly more likely and severe residual weakness less likely with plasma exchange.

• Intravenous immunoglobulin:¹²

  • A Cochrane review found evidence that, in severe disease, intravenous immunoglobulin started within two weeks from the onset hastens recovery as much as plasma exchange.

  • Intravenous immunoglobulin is significantly much more likely to be completed than plasma exchange.

  • Giving intravenous immunoglobulin after plasma exchange did not confer significant extra benefit.

• Corticosteroids: moderate-quality evidence suggests that corticosteroids given alone do not significantly hasten recovery from Guillain-Barré syndrome or affect the long-term outcome; they may even delay recovery.¹³

• Deep vein thrombosis (DVT) prophylaxis: DVT due to immobility should be prevented with gradient compression stockings and subcutaneous low molecular weight heparin. See the separate Prevention of Venous Thromboembolism article.

• Admission to the intensive care unit (ICU): intubation and assisted ventilation may be required.

• Pain relief: may be required for neuropathic pain.

When to admit the patient to the intensive care unit

Reasons for considering admission to ICU include:⁸

• Rapid progression of weakness.

• Evolving respiratory distress with imminent respiratory insufficiency.

• Severe autonomic cardiovascular dysfunction (such as arrhythmias or marked variation in blood pressure).

• Severe problems swallowing or reduced cough reflex.

Complications

Possible complications include:

• Persistent paralysis.

• Respiratory failure requiring mechanical ventilation.

• Hypotension or hypertension.

• Thromboembolism, pneumonia, skin breakdown.

• Cardiac arrhythmia.

• Ileus.

• Aspiration pneumonia.

• Urinary retention.

• Psychiatric problems - eg, depression, anxiety.

Prognosis

• The outcome for most patients with GBS, even those who required mechanical ventilation at the peak of severity, is generally good.

• About 80% of patients can walk independently at six months after the onset of disease.¹

• However, neurological problems persist in up to 20% of patients; half of these patients are severely disabled.¹⁴

• The mortality rate is estimated to be 3-10%.¹⁵ Death tends to be due to respiratory failure, pulmonary emboli or infection.

• Poor prognosis is associated with rapid progression of symptoms, advanced age and prolonged ventilation.

• High age, preceding diarrhoea, and degree of muscle dysfunction at hospital admission and at one week are independently associated with being unable to walk at four weeks, three months and six months.¹⁶