Elsevier

The Lancet

Volume 388, Issue 10045, 13–19 August 2016, Pages 717-727
The Lancet

Seminar
Guillain-Barré syndrome

https://doi.org/10.1016/S0140-6736(16)00339-1Get rights and content

Summary

Guillain-Barré syndrome is the most common and most severe acute paralytic neuropathy, with about 100 000 people developing the disorder every year worldwide. Under the umbrella term of Guillain-Barré syndrome are several recognisable variants with distinct clinical and pathological features. The severe, generalised manifestation of Guillain-Barré syndrome with respiratory failure affects 20–30% of cases. Treatment with intravenous immunoglobulin or plasma exchange is the optimal management approach, alongside supportive care. Understanding of the infectious triggers and immunological and pathological mechanisms has advanced substantially in the past 10 years, and is guiding clinical trials investigating new treatments. Investigators of large, worldwide, collaborative studies of the spectrum of Guillain-Barré syndrome are accruing data for clinical and biological databases to inform the development of outcome predictors and disease biomarkers. Such studies are transforming the clinical and scientific landscape of acute autoimmune neuropathies.

Introduction

The clinical journey through Guillain-Barré syndrome follows a typical pattern that can be readily divided into its constituent phases and components (figure 1).1 Demyelinating and axonal forms of the syndrome occur in varying proportions across different geographical regions, and clinical variants, such as Miller Fisher syndrome, are readily definable.2 Within the typical disease course are many less well understood biological variations, which are considered chronologically in this Seminar.

First, Guillain-Barré syndrome is usually preceded by infection or other immune stimulation that induces an aberrant autoimmune response targeting peripheral nerves and their spinal roots.3, 4 Molecular mimicry between microbial and nerve antigens is clearly a major driving force behind the development of the disorder, at least in the case of Campylobacter jejuni infection. However, the interplay between microbial and host factors that dictates if and how the immune response is shifted towards unwanted autoreactivity is still not well understood.5 Furthermore, genetic and environmental factors that affect an individual's susceptibility to develop the disease are unknown.6 Unwanted autoimmunity does not arise in most individuals (>99%) exposed to an immune stimulus as a result of Guillain-Barré syndrome-associated infections such as C jejuni.7

The acute progression of limb weakness, often with sensory and cranial nerve involvement 1–2 weeks after immune stimulation, proceeds to its peak clinical deficit in 2–4 weeks.8 When patients present with rapidly progressive paralysis, the diagnosis of Guillain-Barré syndrome needs to be made as soon as possible. Although establishment of the diagnosis in typical cases is usually straightforward, there are many clinical and investigative components to consider, especially in atypical cases. The diagnosis is largely based on clinical patterns, because diagnostic biomarkers are not available for most variants of the syndrome. Identification of biomarkers and establishment of their pathophysiological roles, if any, in experimental models has been a major research challenge.9, 10 All patients with Guillain-Barré syndrome need meticulous monitoring and supportive care.11 Early initiation of intravenous immunoglobulins (IVIg) or plasma exchange is of proven benefit and crucial, especially in patients with rapidly progressive weakness.12 Because a quarter of patients need artificial ventilation and many develop autonomic disturbances, many patients need admission in the high or intensive care setting. Symptoms peak within 4 weeks, followed by a recovery period that can last months or years, as the immune response decays and the peripheral nerve undergoes an endogenous repair process.

Efforts focus on the measurement and prediction of clinical course and outcome to improve the care and treatment of individual patients.13 Good prognostic models have been developed, but additional studies are needed to investigate whether these prognostic factors differ between different disease subgroups and areas in the world. In parallel, prognostic biomarkers now need to be developed to better predict outcomes and guide action, such as personalised treatment refinements in acute management.14 Finally, the impact of Guillain-Barré syndrome on individuals and as a global health issue is discussed alongside efforts to create evidence-based uniformity in the management of affected patients in different health-care settings.

Section snippets

Epidemiology and preceding infections

Most studies that estimate incidence rates of Guillain-Barré syndrome were done in Europe and North America, and showed a similar range of 0·8–1·9 (median 1·1) cases per 100 000 people per year.15 The annual incidence rate of Guillain-Barré syndrome increases with age (0·6 per 100 000 per year in children and 2·7 per 100 000 per year in elderly people aged 80 years and over) and the disease is slightly more frequent in males than in females. Seasonal fluctuations, presumably related to

Pathophysiology and immunopathology

Until 20 years ago Guillain-Barré syndrome was regarded as a homogeneous disorder, the outcome of which varied according to severity. This variation was believed to be largely caused by the extent of bystander axonal injury arising secondarily to adjacent demyelination, rather than fundamental pathophysiological differences in the types of Guillain-Barré syndrome between individuals.36 Peripheral nerve remyelination is a functionally effective, natural repair process, whereas axonal

Clinical classification and diagnosis

In typical Guillain-Barré syndrome, rapidly progressive bilateral weakness is the key presenting symptom in most patients (panel 1).1, 8, 65, 66 Weakness is classically described as ascending, and usually starts in the distal lower extremities, but can start more proximally in the legs or arms. The latter pattern can give the false clinical impression of a pyramidal lesion (ie, at the level of the spinal cord or above), but can be easily explained by focal conduction block at the level of the

Variants, formes frustes, and paediatric presentations

Guillain-Barré syndrome is a remarkably clinically diverse disorder and includes several clinically distinctive variants, formes frustes, and atypical cases. The frequency of these variant forms in part relates to the geographical area in which the disease is reported. Guillain-Barré syndrome can be restricted to specific nerve fibres, as 15% of patients with a pure motor form do not have any sensory deficits.4 Pure motor Guillain-Barré syndrome can occur both in patients with acute motor

Electrophysiological classification: current considerations

Guillain-Barré syndrome is a clinically diagnosed disorder, but nerve conduction studies (NCS) can help to support the diagnosis, to discriminate between axonal and demyelinating subtypes, and could relate to prognosis. Nerve conduction abnormalities are most pronounced 2 weeks after start of weakness.58 NCS findings can be normal especially early in the course of disease. To increase the diagnostic yield, at least four motor nerves, three sensory nerves, F-waves, and H-reflexes, should be

Approaches to treatment and clinical trials

Guillain-Barré syndrome is a potentially life-threatening disease. Both general medical care and immunological treatment are essential (figure 3). Meticulous attention to supportive care is needed to prevent or to manage complications.4, 11 Measures include monitoring of respiratory function by frequent measurement of vital capacity and other clinical outcomes, and timely transfer to ICU when needed. To help this decision making process, the Erasmus GBS Respiratory Insufficiency Score (EGRIS)

TRFs and acute onset chronic inflammatory demyelinating neuropathy

About 10% of patients treated with IVIg or plasma exchange will deteriorate after initial improvement or stabilisation—ie, they will have a TRF.12, 92 These TRFs usually occur within the first 8 weeks after start of treatment. Repeated treatment (2 g IVIg/kg in 2–5 days) has been observed to be beneficial in these patients. Although no RCTs have shown that re-treatment is beneficial in case of a TRF, it is common practice in many centres to do so.66 Patients with Guillain-Barré syndrome with a

Outcome and prediction of outcome

Guillain-Barré syndrome is still a life-threatening disorder with frequent morbidities, even with the best treatment available. Mortality rates in Europe and North America vary between 3% and 7%, and more widely in other countries where data are available.23, 94, 95, 96 Patients can die in the acute progressive stage, most probably because of ventilatory insufficiency or pulmonary complications, or from autonomic dysfunction including arrhythmia. However, death can occur at a late stage when a

Conclusions

In 2016, we approach the centenary of the first description of Guillain-Barré syndrome with some comfort in the knowledge that our rapidly advancing understanding of the pathological mechanisms of the disease is informing new treatment strategies and approaches to clinical care.103 Treatments have been developed and proved effective, but these are not sufficient in many patients. Although there have been major steps forward, this is no time for complacency as the research area continues to face

Search strategy and selection criteria

We searched the entire Cochrane Library, MEDLINE, and PubMed using the search term “Guillain-Barré syndrome”. We mainly selected publications from the past 5 years, but did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of articles identified by this search strategy and selected those papers we judged relevant. Review articles are cited to provide readers with more details and references than can be provided in this Seminar.

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