Guillain-Barré Syndrome

Synonym: acute inflammatory polyneuritis

Guillain-Barré syndrome is disorder causing demyelination and axonal degeneration resulting in acute, ascending and progressive neuropathy, characterised by weakness, paraesthesiae, and hyporeflexia. About 75% of patients have a history of preceding infection, usually of the respiratory and gastrointestinal tract. A large number of infections have been linked, including Campylobacter jejuni, Epstein Barr virus, cytomegalovirus, mycoplasma and human immunodeficiency virus.^1,2 This association with preceding infection suggests that antibodies to the infectious organism also attack antigens in peripheral nerve tissue.

The closest association between antibodies and the neurological disease is seen with the closely related Miller Fisher syndrome (also called Fisher 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 have features of the Miller Fisher syndrome, but with associated weakness.¹

Guillain-Barré syndrome consists of a number of subtypes, including:³

• Acute inflammatory demyelinating polyradiculoneuropathy (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 acute inflammatory demyelinating polyradiculoneuropathy.

• The incidence of typical Guillain-Barré syndrome in Europe is 1.2-1.9 per 100,000.³
• There is an increased incidence in males. Peak ages are 15-35 years and 50-75 years.⁴

Risk factors

• History of gastrointestinal or respiratory infection from 1-3 weeks prior to the onset of weakness.
• Vaccinations: live and dead vaccines have been implicated.
• Malignancies, e.g. lymphomas, especially Hodgkin's disease.
• Pregnancy: incidence decreases during pregnancy but increases in the months after delivery.⁴

History

• Weakness:
  • In 60% of cases, onset occurs approximately three weeks after a viral illness.
  • The condition usually presents with an ascending pattern of progressive symmetrical weakness, starting in the lower extremities.
  • This reaches a level of maximum severity 2 weeks after initial onset of symptoms and usually stops progressing after 5 weeks.
  • 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 and urinary hesitancy. Severe autonomic dysfunction may occur.

Examination

The following features may be present:

• Hypotonia.
• Demonstrable altered sensation or numbness.
• Reduced or absent reflexes.
• Facial weakness - may be asymmetrical.
• Autonomic dysfunction - fluctuations of heart rate and arrhythmias, labile blood pressure and variable temperature.
• Respiratory muscle paralysis.

Other causes of acute paralysis include:

• Brain: stroke, brainstem compression, encephalitis.
• Spinal cord: cord compression, poliomyelitis, transverse myelitis.
• Peripheral nerve: vasculitis, lead poisoning, porphyria.
• Neuromuscular junction: myasthenia gravis, botulism.
• Muscle: hypokalaemia, polymyositis.

Diagnosis usually is made on clinical grounds. However, the following may be helpful:

• Electrolytes: inappropriate antidiuretic hormone secretion occurs in some patients, serum and urine osmolarity studies are indicated if it is suspected.
• 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.
• Antibody screen: antibodies to peripheral and central nerves may be present.
• Spirometry: forced vital capacity is a major determinant on the need for admission to ICU and then the need for intubation.
• Nerve conduction studies: are the most useful confirmatory test and are abnormal in 85% of patients, even early on in the disease. They should be repeated after two weeks if they are initially normal.¹ A decrease to less than 20% of predicted normal is associated with a poorer prognosis.
• ECG: many different abnormalities may be seen, e.g. 2^nd and 3^rd degree AV block, T wave abnormalities, ST depression, QRS widening and a variety of rhythm disturbances.

• Plasma exchange: plasma exchange is more beneficial when started within seven days after disease onset rather than later, but has been shown to still be beneficial in patients treated up to 30 days after disease onset.⁵
• Intravenous immunoglobulin: this was also examined in a Cochrane review and found to be as effective as plasma exchange. There was no benefit in combining the two treatments.⁶
• Intravenous methylprednisolone: substantial evidence shows that intravenous methylprednisolone alone does not produce significant benefit or harm. In combination with intravenous immunoglobulin, intravenous methylprednisolone may hasten recovery but does not significantly affect the long-term outcome.⁷
• Deep vein thrombosis (DVT) prophylaxis: DVT due to immobility should be prevented with gradient compression stockings and subcutaneous low molecular weight heparin. See Prevention of Deep Vein Thrombosis article.
• Admission to the intensive-care unit: intubation and assisted ventilation may be required.

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, e.g. depression, anxiety

• With modern intensive care support, the outcome is excellent for most patients.⁸
• However about 20% of patients have residual disability, with weakness or persistent sensory disturbance.
• About 10% of patients die from respiratory failure, pulmonary emboli or infection.¹
• Mortality may also occur as a result of severe autonomic instability or from the complications of prolonged intubation and paralysis.
• In severe cases, there is a higher frequency of persistent neurological dysfunction but the majority of this group make a good functional recovery.
• Poor prognosis is associated with rapid progression of symptoms, advanced age and prolonged ventilation.
• Patients with Miller Fisher syndrome generally recover within 1-3 months.⁴

1. Winer JB; Guillain-Barre syndrome. BMJ. 2008 Jul 17;337:a671. doi: 10.1136/bmj.a671.
2. Kuwabara S; Guillain-Barre syndrome: epidemiology, pathophysiology and management. Drugs. 2004;64(6):597-610. [abstract]
3. Hughes RA, Cornblath DR; Guillain-Barre syndrome. Lancet. 2005 Nov 5;366(9497):1653-66. [abstract]
4. Miller A, Ali O; Guillain-Barre Syndrome; eMedicine, July 2009.
5. Raphael JC, Chevret S, Hughes RA, et al; Plasma exchange for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2002;(2):CD001798. [abstract]
6. Hughes RA, Raphael JC, Swan AV, et al; Intravenous immunoglobulin for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD002063. [abstract]
7. Hughes RA, Swan AV, van Koningsveld R, et al; Corticosteroids for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001446. [abstract]
8. Hund EF, Borel CO, Cornblath DR, et al; Intensive management and treatment of severe Guillain-Barre syndrome. Crit Care Med. 1993 Mar;21(3):433-46. [abstract]

• Guillain-Barré Syndrome Support Group