Guillain-Barré Syndrome Animal Model: The First Proof of Molecular Mimicry in Human Autoimmune Disorder

Molecular mimicry between self and microbial components has been proposed as the pathogenic mechanism of autoimmune diseases, and this hypothesis is proven in Guillain-Barré syndrome. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, sometimes occurs after Campylobacter jejuni enteritis. Gangliosides are predominantly cell-surface glycolipids highly expressed in nervous tissue, whilst lipo-oligosaccharides are major components of the Gram-negative bacterium C. jejuni outer membrane. IgG autoantibodies to GM1 ganglioside were found in the sera from patients with Guillain-Barré syndrome. Molecular mimicry was demonstrated between GM1 and lipo-oligosaccharide of C. jejuni isolated from the patients. Disease models by sensitization of rabbits with GM1 and C. jejuni lipo-oligosaccharide were established. Guillain-Barré syndrome provided the first verification that an autoimmune disease is triggered by molecular mimicry. Its disease models are helpful to further understand the molecular pathogenesis as well as to develop new treatments in Guillain-Barré syndrome

Diagnosis and management of Guillain-Barré syndrome in ten steps

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae

Guía basada en la evidencia. Diagnóstico y manejo del síndrome de Guillain-Barré en diez pasos = Evidence based guidelines. Diagnosis and management of Guillain-Barré syndrome in ten steps

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae

Diagnosis and management of Guillain–Barré syndrome in ten steps

Guillain–Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae

Understanding the pathogenesis of guillain-barre syndrome through neurophysiology and serological analyses / Nortina Shahrizaila

Guillain-Barré syndrome (GBS) is the leading cause of post-infectious flaccid paralysis worldwide. Over the years, research on the neurophysiological characteristics and serological profile of GBS patients has contributed towards our greater understanding of its pathogenesis. GBS can be classified into demyelinating and axonal subtypes, based on their neurophysiological features. In axonal GBS, antibodies against several glycolipids have been identified whereas target antigens in demyelinating GBS remain unknown. In this thesis, a series of published original work addressing the current limitations in GBS electrodiagnosis and serological associations with disease features are presented. In the first series of publications, prospective serial nerve conduction studies (NCS) in a cohort of multi-ethnic Malaysian GBS patients are described. We found that in order to make a true electrodiagnosis of GBS, at least two sets of NCS were required performed with the first 2 weeks of disease onset and 3 to 8 weeks later. Based on NCS, we also found an almost exclusive involvement of sensory fibres in patients with the GBS variant, Miller Fisher syndrome irrespective of their symptoms. The second series of publication investigated the presence of antibodies against glycolipid complexes in GBS patients from Asian and Western cohorts. The relationship between these antibodies and the clinical features as well as neurophysiological characteristics of GBS based on serial NCS was also investigated. Our studies provided robust evidence that antibodies to single glycolipids and glycolipid complexes are associated with axonal forms of GBS and not acute inflammatory demyelinating polyneuropathy. Future studies incorporating standardized methods of neurophysiological assessment and serological analyses in heterogeneous populations are required to better understand GBS pathophysiology. Existing on-going international research collaboration is one platform in which findings from the current work can be further validated

Guillain-Barre syndrome

Guillain-Barre 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-Barre syndrome, most notably Campylobacter jejuni, Zika virus, and in 2020, the severe acute respiratory syndrome coronavirus 2. In C jejuni-related Guillain-Barre 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-Barre 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-Barre syndrome do well with immunotherapy, but a substantial proportion are left with disability, and death can occur. Results from the International Guillain-Barre Syndrome Outcome Study suggest that geographical variations exist in Guillain-Barre 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-Barre 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

Optimizing the electrodiagnostic accuracy in Guillain-Barré syndrome subtypes: Criteria sets and sparse linear discriminant analysis

Objective To optimize the electrodiagnosis of Guillain-Barré syndrome (GBS) subtypes at first study. Methods The reference electrodiagnosis was obtained in 53 demyelinating and 45 axonal GBS patients on the basis of two serial studies and results of anti-ganglioside antibodies assay. We retrospectively employed sparse linear discriminant analysis (LDA), two existing electrodiagnostic criteria sets (Hadden et al., 1998; Rajabally et al., 2015) and one we propose that additionally evaluates duration of motor responses, sural sparing pattern and defines reversible conduction failure (RCF) in motor and sensory nerves at second study. Results At first study the misclassification error rates, compared to reference diagnoses, were: 15.3% for sparse LDA, 30% for our criteria, 45% for Rajabally's and 48% for Hadden's. Sparse LDA identified seven most powerful electrophysiological variables differentiating demyelinating and axonal subtypes and assigned to each patient the diagnostic probability of belonging to either subtype. At second study 46.6% of axonal GBS patients showed RCF in two motor and 8.8% in two sensory nerves. Conclusions Based on a single study, sparse LDA showed the highest diagnostic accuracy. RCF is present in a considerable percentage of axonal patients. Significance Sparse LDA, a supervised statistical method of classification, should be introduced in the electrodiagnostic practice