Elsevier

The Lancet

Volume 397, Issue 10280, 27 March–2 April 2021, Pages 1214-1228
The Lancet

Seminar
Guillain-Barré syndrome

https://doi.org/10.1016/S0140-6736(21)00517-1Get rights and content

Summary

Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Most patients present with an antecedent illness, most commonly upper respiratory tract infection, before the onset of progressive motor weakness. Several microorganisms have been associated with Guillain-Barré syndrome, most notably Campylobacter jejuni, Zika virus, and in 2020, the severe acute respiratory syndrome coronavirus 2. In C jejuni-related Guillain-Barré syndrome, there is good evidence to support an autoantibody-mediated immune process that is triggered by molecular mimicry between structural components of peripheral nerves and the microorganism. Making a diagnosis of so-called classical Guillain-Barré syndrome is straightforward; however, the existing diagnostic criteria have limitations and can result in some variants of the syndrome being missed. Most patients with Guillain-Barré syndrome do well with immunotherapy, but a substantial proportion are left with disability, and death can occur. Results from the International Guillain-Barré Syndrome Outcome Study suggest that geographical variations exist in Guillain-Barré syndrome, including insufficient access to immunotherapy in low-income countries. There is a need to provide improved access to treatment for all patients with Guillain-Barré syndrome, and to develop effective disease-modifying therapies that can limit the extent of nerve injury. Clinical trials are currently underway to investigate some of the potential therapeutic candidates, including complement inhibitors, which, together with emerging data from large international collaborative studies on the syndrome, will contribute substantially to understanding the many facets of this disease.

Introduction

Guillain-Barré syndrome is an immune-mediated polyradiculoneuropathy that accounts for an estimated 100 000 new cases annually worldwide.1 In most patients, the acute onset of neurological symptoms is preceded by an infective illness,2 followed by progressive limb weakness, which can last up to 4 weeks before reaching plateau. Several infections are associated with Guillain-Barré syndrome, but Campylobacter jejuni is the most common and extensively reported.3 In C jejuni-related Guillain-Barré syndrome, robust evidence suggests that molecular mimicry exists between nerve and microbial antigens, leading to the development of Guillain-Barré syndrome.4

The classic presentation of the syndrome does not typically pose a diagnostic challenge, but atypical variants are missed when not considered. To support diagnosis, polyradiculoneuropathy can be detected on nerve conduction studies, and cerebrospinal fluid analysis can show albumincytological dissociation, although both tests can be normal in the early stages.5 Patients with Guillain-Barré syndrome require close monitoring for disease progression, in particular for bulbar weakness, respiratory insufficiency, and autonomic dysfunction. Prognostic scales have been developed to predict patient outcome and to stratify treatment. To date, intravenous immunoglobulin and plasma exchange are the only recognised immunotherapeutic drugs that can accelerate recovery in Guillain-Barré syndrome.5 However, the syndrome is still a serious disease. Even when treated with standard immunotherapies, approximately 5% of people die, and up to 20% cannot walk independently at 1 year from disease onset.

The past 5 years have seen advances in our understanding of Guillain-Barré syndrome, which is the focus of this Seminar. We now have improved understanding of Zika virus-associated Guillain-Barré syndrome,6 improved insight into the global burden of the syndrome through the International Guillain-Barré Syndrome Outcome Study (IGOS),7 and new therapeutic drugs have entered early clinical development.

Section snippets

Epidemiology

Guillain-Barré syndrome has been reported in many countries and has a wide range of reported incidences (figure 1).1, 8 Population-based studies from North America and Europe suggest that incidence ranges from 0·81 to 1·91 cases per 100 000 person-years (median 1·11). There is a 20% increase in incidence for every 10-year increase in age, and unlike other autoimmune diseases, the risk of Guillain-Barré syndrome is higher in men than in women.1

Although not designed to study populations, IGOS

Overview

Up to the late 1980s, Guillain-Barré syndrome was considered to be a single disease entity with immune-mediated attack on myelin components, resulting in demyelination and secondary axonal damage. It subsequently became clear that Guillain-Barré syndrome could be broadly classified into acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and AMAN, depending on the site of target antigen.25, 56 This classification, together with the discovery of antiglycolipid antibodies, expanded the

Approach to treatment

The management of patients with Guillain-Barré syndrome can be stratified according to the different stages of the disease (figure 3). In the acute phase, typically within the first 2 weeks of disease onset, patients are at risk of developing complications and extensive nerve damage. In patients with potential respiratory and autonomic failure, admission to a high-dependency unit is advisable for close monitoring of disease progression. Immunotherapy should be initiated as soon as patients show

Controversies, uncertainties, and future directions

Despite the advances in the understanding of Guillain-Barré syndrome, many uncertainties remain. To date, IGOS has impressively recruited almost 2000 patients with Guillain-Barré syndrome, but most patients have been recruited from high-income countries. Published data on Guillain-Barré syndrome in Africa, the Middle East, and many parts of Asia are scarce. To fully comprehend the global burden of Guillain-Barré syndrome and factors associated with the disease, active global engagement with

Conclusion

Since its initial description in 1916 by Georges Guillain, Jean Alexandre Barré, and André Strohl, there continues to be substantial developments in Guillain-Barré syndrome. IGOS has provided some clarity on geographical variations with more information likely to follow. The transient surge in patients with Guillain-Barré syndrome during the 2016 Zika virus outbreak and emerging reports of Guillain-Barré syndrome in SARS-CoV-2 infection add to the growing list of antecedent infections. With the

Search strategy and selection criteria

We searched the Cochrane Library, MEDLINE, and PubMed using the search term “Guillain-Barré syndrome”. Publications from January, 2015, to April, 2020, were primarily selected, but we also included older publications that provided some of the seminal works in Guillain-Barré syndrome. We also searched the reference lists of articles identified by this search strategy, and selected papers that were relevant to the subject matter. Review articles are cited to provide readers with more details and

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