Update on Guillain‐Barré syndrome

Abstract

Understanding of Guillain-Barré syndrome (GBS) has progressed substantially since the seminal 1916 report by Guillain et al. Although Guillain, Barré, and Strohl summarised the syndrome based on observations of two French infantrymen, 2012 saw the beginning of an ambitious collaborative study designed to collect detailed data from at least 1,000 patients worldwide (IGOS, www.gbsstudies.org/about-igos). Progress has been made in many areas even since GBS was last reviewed in this journal in 2009. GBS subsequently received prominent attention in light of concerns regarding H1N1 influenza vaccinations, and several large-scale surveillance studies resulted. Despite these developments, and promising pre-clinical studies, disease-modifying therapies for GBS have not substantially altered since intravenous immunoglobulin was introduced over 20 years ago. In other areas, management has improved. Antibiotic prophylaxis in ventilated patients reduces respiratory tract infection, thromboprophylaxis has reduced the risk of venous thromboembolism, and there is increasing awareness of the benefit of high-intensity rehabilitation. This article highlights some of the interesting and thought-provoking developments of the last 3 years, and is based on a plenary lecture given at the 2012 Peripheral Nerve Society (PNS) meeting.

The pathogenic relevance of αM-integrin in Guillain–Barré syndrome

“…Human IVIg-treated mice demonstrated reduced F4/80+ counts compared to PBS and isotype-treated mice (Fig 4b). This study did not evaluate phenotypic shifts from pro-inflammatory M1 to anti-inflammatory M2 macrophages, pro-inflammatory CD4+ Th1/Th17 to anti-inflammatory Th2 or increase in regulatory CD4+ CD25+ FoxP3+ T lymphocytes or alterations in pro-inflammatory and anti-inflammatory/regulatory B-cells that may explain improved clinical course with human IVIg not seen with isotype-treated mice [5,23,28,32]. Representative photomicrographs depicting differences in sciatic nerve inflammation between CD11b antagonism and PBS, human IVIg and isotype-treated sm-EAN mice are shown in Fig 5.…”

“…Several variants exist based on clinical, electrophysiological and pathological characteristics. Its most common variant, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is pathologically characterized by monocyte/macrophage-induced demyelination associated with intense T- and B-lymphocyte infiltration into peripheral nerves and nerve roots [23,28,32]. GBS pathogenesis involves a complex interplay of systemic immune activation (which may be mediated in genetically susceptible individuals via molecular mimicry) with T-lymphocyte activation with polarization, polyclonal B-lymphocyte maturation and immunoglobulin synthesis, and a tissue-restricted immune response characterized by hematogenous leukocyte trafficking across the blood-nerve barrier (BNB), complement-mediated lysis, complement- and antibody-dependent cellular cytotoxicity, cytokine-mediated injury, and Schwann cell innate and adaptive immune response modulation [5,11,14,23,31,40,41,28].…”

“…Despite significant advances in molecular biology and genetics that provide insights into GBS pathogenesis, no new treatments or significant improvements in patient outcomes have occurred over the last 20 years [23,28]. Possible barriers to progress in the field include dearth of patient nerve biopsies for extensive exploratory studies, unavailability of human BNB models to study pathogenic inflammatory mechanisms in vitro and limitations in animal models required to verify pathogenic mechanisms in vivo before clinical trials are planned [14].…”

Inflammatory neuropathies: pathology, molecular markers and targets for specific therapeutic intervention

“…Several excellent reviews on the immunopathogenesis of GBS have been published, highlighting the complexities of systemic immune activation with T lymphocyte activation with polarization towards CD4+ T helper 1 (Th1) and T helper 17 (Th17) phenotypes, with reduction on T helper 2 (Th2) and possible alterations in CD25+ FoxP3+ regulatory T lymphocytes, polyclonal B-cell maturation and immunoglobulin synthesis within primary and secondary lymphoid organs, complement-mediated lysis, monocyte/macrophage and lymphocyte-mediated demyelination via cytokines, as well as complement- and antibody-dependent cellular cytotoxicity, Schwann cell roles in potentiating the local innate and adaptive immune response as well as in terminating inflammation by inducing T lymphocyte apoptosis [26,65,86,114,137,159,161]. Hematogenous leukocyte trafficking and immunoglobulin transport across the blood-nerve barrier (BNB; formed by tight junction forming microvascular endothelium within peripheral nerve and nerve root endoneurium) are commonly depicted; however, very little is known about pathologic leukocyte-BNB endothelial interactions and BNB permeability changes that occur in AIDP.…”

Expression of Early Growth Response Gene-2 and Regulated Cytokines Correlates with Recovery from Guillain–Barré Syndrome

“…Animal models of autoinmune diseases using rats, mice, and rabbits have improved our understanding of the pathogenesis of GBS and other autoimmune neuropathies and have facilitated testing the potential for therapies based on the manipulation of the immune system (22)(23)(24)(25). However, none of the animal models mimic all the features of GBS but rather reflect specific facets of the syndrome (26).…”