Elsevier

The Lancet

Volume 366, Issue 9497, 5–11 November 2005, Pages 1653-1666
The Lancet

Seminar
Guillain-Barré syndrome

https://doi.org/10.1016/S0140-6736(05)67665-9Get rights and content

Summary

Guillain-Barré syndrome consists of at least four subtypes of acute peripheral neuropathy. Major advances have been made in understanding the mechanisms of some of the subtypes. The histological appearance of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype resembles experimental autoimmune neuritis, which is predominantly caused by T cells directed against peptides from the myelin proteins P0, P2, and PMP22. The role of T-cell-mediated immunity in AIDP remains unclear and there is evidence for the involvement of antibodies and complement. Strong evidence now exists that axonal subtypes of Guillain-Barré syndrome, acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN), are caused by antibodies to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier. About a quarter of patients with Guillain-Barré syndrome have had a recent Campylobacter jejuni infection, and axonal forms of the disease are especially common in these people. The lipo-oligosaccharide from the C jejuni bacterial wall contains ganglioside-like structures and its injection into rabbits induces a neuropathy that resembles acute motor axonal neuropathy. Antibodies to GM1, GM1b, GD1a, and GalNac-GD1a are in particular implicated in acute motor axonal neuropathy and, with the exception of GalNacGD1a, in acute motor and sensory axonal neuropathy. The Fisher's syndrome subtype is especially associated with antibodies to GQ1b, and similar cross-reactivity with ganglioside structures in the wall of C jejuni has been discovered. Anti-GQ1b antibodies have been shown to damage the motor nerve terminal in vitro by a complement-mediated mechanism. Results of international randomised trials have shown equivalent efficacy of both plasma exchange and intravenous immunoglobulin, but not corticosteroids, in hastening recovery from Guillain-Barré syndrome. Further research is needed to discover treatments to prevent 20% of patients from being left with persistent and significant disability.

Section snippets

Worldwide incidence

The incidence of typical Guillain-Barré syndrome has been reported to be relatively uniform between 0·6 and four cases per 100 000 per year throughout the world,16 but the most recent and careful population-based studies in Europe consistently report an incidence of 1·2–1·9 per 100 000.17, 18, 19, 20, 21, 22 Atypical cases such as Fisher's syndrome are much less common and Italian researchers have reported an incidence of 0·1 per 100 000.18 All reports agree that men are about 1·5 times more

Diagnosis

The diagnosis of Guillain-Barré syndrome itself is usually not difficult for the neurologist, but can be challenging for the doctor of first contact who may not have seen a case since medical school. Established diagnostic criteria exist and have stood the test of time.37 Most patients will have an acute neuropathy reaching a peak in under 4 weeks, weakness, hyporeflexia or areflexia, and raised protein concentrations in CSF. However, the rapid development of inexplicable weakness in a patient

Neurophysiological testing

Neurophysiological studies play a very important role in diagnosis, subtype classification, and confirmation that the disease is a peripheral neuropathy (panel 2).9, 45 Sufficient information is required: usually, this would include data from at least three sensory nerves, at least three motor nerves with multisite stimulation and F waves, and bilateral tibial H-reflexes. In some cases, information from a smaller number of nerves may suffice. With this neurophysiological information, individual

Investigations

In addition to neurophysiological testing, a lumbar puncture procedure is traditional and almost always appropriate. A raised CSF protein concentration is present in about 80% of patients, but CSF protein content is more likely to be normal during the first days of the illness.10, 14 CSF should be analysed before treatment with intravenous immunoglobulin (IVIg), which can cause aseptic meningitis. Other investigations may be needed to exclude causes of similar illnesses or to identify

AIDP

The classic pathological picture of Guillain-Barré syndrome is of multifocal mononuclear cell infiltration throughout the peripheral nervous system in which the distribution of inflammation corresponds to the clinical deficit.3 Macrophages invade the myelin sheaths and denude the axons. For the most part, macrophages seem to invade intact myelin sheaths (figure 1), as occurs in experimental autoimmune neuritis.4, 63, 64 According to one hypothesis, the activated macrophages are targeted to

Clinical course

In typical cases, the first symptoms are pain, numbness, paraesthesia, or weakness in the limbs. The weakness may initially be proximal, distal, or a combination of both. Numbness and paraesthesia usually affect the extremities and spread proximally. In children, pain may be a prominent presenting symptom. The facial nerves are often affected and less often the bulbar and ocular motor nerves. In 25% of cases, weakness of the respiratory muscles requires artificial ventilation. Autonomic

Prognosis

From the many case series, and especially from population-based studies that have investigated possible prognostic factors, the most consistent finding has been that the outlook is worse in elderly patients.9, 19, 140 In children, recovery is more rapid and more likely to be complete; death is exceptional.143, 144 In adults and children, severity of disease at nadir, expressed as being bedbound or requiring artificial ventilation, has usually been identified as an adverse prognostic factor.140

General treatment

Excellent multidisciplinary care is needed to prevent and manage the potentially fatal complications of the disease, and the methods have been the subject of a consensus report.147 Respiratory failure occurs in 25% of patients and is more likely in cases with rapid progression, bulbar palsy, upper limb involvement, and autonomic dysfunction. Regular monitoring, including measurement of vital capacity, and early transfer to an intensive therapy unit for prophylactic intubation are essential. All

Immunotherapy

Plasma exchange became accepted as the gold standard treatment for Guillain-Barré syndrome almost 20 years ago. Evidence to support this practice has accumulated from six trials, but not all studies provided all the outcome measures of interest. Most used a 7-point Guillain-Barré syndrome disability grade scale. In four trials, including 585 participants with available data, plasma exchange increased the improvement after 4 weeks by an average of 0·89 grades (95% CI 0·63–1·14). In five trials

Search strategy and selection criteria

For the sections on pathogenesis and diagnosis, we searched MEDLINE and EMBASE in all languages on Nov 4, 2004, and our personal databases, using the search term “Guillain-Barré syndome”. For the sections on treatment, we searched the Cochrane Library and made use of the relevant Cochrane reviews which themselves used the published search strategy and methods for selecting evidence of the Cochrane Neuromuscular Disease Group.

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