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Axonal variants of Guillain-Barre syndrome (GBS) mainly include acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and pharyngeal-cervical-brachial weakness. Molecular mimicry of human gangliosides by a pathogen's lipooligosaccharides is a well-established mechanism for Campylobacter jejuni-associated GBS. New triggers of the axonal variants of GBS (axonal GBS), such as Zika virus, hepatitis viruses, intravenous administration of ganglioside, vaccination, and surgery, are being identified. However, the pathogenetic mechanisms of axonal GBS related to antecedent bacterial or viral infections other than Campylobacter jejuni remain unknown. Currently, autoantibody classification and serial electrophysiology are cardinal approaches to differentiate axonal GBS from the prototype of GBS, acute inflammatory demyelinating polyneuropathy. Newly developed technologies, including metabolite analysis, peripheral nerve ultrasound, and feature selection via artificial intelligence are facilitating more accurate diagnosis of axonal GBS. Nevertheless, some key issues, such as genetic susceptibilities, remain unanswered and moreover, current therapies bear limitations. Although several therapies have shown considerable benefits to experimental animals, randomized controlled trials are still needed to validate their efficacy.

Introduction: Up to 30% of patients with Guillain-Barre syndrome (GBS) develop respiratory failure requiring intensive care unit (ICU) admission and mechanical ventilation. Progressive weakness of the respiratory muscles is the leading cause of acute respiratory distress and respiratory failure with hypoxia and/or hypercarbia. Bulbar weakness may compromise airway patency and predispose patients to aspiration pneumonia. Areas covered: Clinical questions related to the use of mechanical ventilation include but are not limited to: When to start? Invasive or noninvasive? When to wean from mechanical ventilation? When to perform tracheostomy? How to manage complications of GBS in the ICU including nosocomial infection, ventilator-associated pneumonia, and ICU-acquired weakness? In this narrative review, the authors summarize the up-to-date knowledge of the incidence, pathophysiology, evaluation, and general management of respiratory failure in GBS. Expert opinion: Respiratory failure in GBS merits more attention from caregivers. Emergency intubation may lead to life-threatening complications. Appropriate methods and time point of intubation and weaning, an early tracheostomy, and predictive prophylaxis of complications benefit patients' long-term prognosis.

Guillain–Barré syndrome (GBS) is an acute polyneuropathy mostly characterized by acute flaccid paralysis with or without sensory/autonomous nerve dysfunction. Current immuno therapies including intravenous immunoglobulin (IVIg), plasma exchange (PE), and newly developed biological drugs benefit patients by alleviating hyperreactive immune responses. Up to 30% of patients develop respiratory failure during hospitalization and require mechanical ventilation and intensive care. Immunotherapies, mechanical ventilation, supportive care, and complication management during the intensive care unit (ICU) stay are equally emphasized. The most important aspect of intensive care and treatment of severe GBS, that is, mechanical ventilation, has been extensively reviewed elsewhere. In contrast to immunotherapies, care and treatment of GBS in the ICU setting are largely empirical. In this review, we intend to stress the importance of intensive care and treatment, other than mechanical ventilation in patients with severe GBS. We summarize the up-to-date knowledge of pharmacological therapies and ICU management of patients with severe GBS. We aim to answer some key clinical questions related to the management of severe GBS patients including but not limited to: Is IVIg better than PE or vice versa? Whether combinations of immune therapies benefit more? How about the emerging therapies promising for GBS? When to perform tracheal intubation or tracheostomy? How to provide multidisciplinary supportive care for severe cases? How to avert life-threatening complications in severe cases?

IntroductionThe aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN).Material and methodsWe selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 µg P0 peptide 180–199 emulsion in 25 µl of PBS and 0.5 mg Mycobacterium tuberculosis (Difco, USA) in 25 µl of Freund’s incomplete adjuvant into the back of mice. The concentrations of serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) were determined using the Ms Th1/Th2/Th17 CBA kit.ResultsWe found that TLR4 deficiency could attenuate the clinical severity and delay the onset of EAN. Moreover, our data showed that the sera levels of IFN-γ, TNF, IL-6 and IL-17A were elevated in the WT mice with EAN when compared with the naive WT mice, but only the production of IL-17A was significantly lower in the TLR4 KO mice with EAN than in their WT counterparts.ConclusionsBased on these findings, TLR4 may contribute to the pathogenesis of EAN by regulating Th17 cells and the production of Th17-associated factors. However, the exact mechanism remains unclear and more evidence is needed to elucidate its role in EAN.

Axonal variants of Guillain-Barré syndrome (GBS) mainly include acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and pharyngeal-cervical-brachial weakness. Molecular mimicry of human gangliosides by a pathogen's lipooligosaccharides is a well-established mechanism for Campylobacter jejuni-associated GBS. New triggers of the axonal variants of GBS (axonal GBS), such as Zika virus, hepatitis viruses, intravenous administration of ganglioside, vaccination, and surgery, are being identified. However, the pathogenetic mechanisms of axonal GBS related to antecedent bacterial or viral infections other than Campylobacter jejuni remain unknown. Currently, autoantibody classification and serial electrophysiology are cardinal approaches to differentiate axonal GBS from the prototype of GBS, acute inflammatory demyelinating polyneuropathy. Newly developed technologies, including metabolite analysis, peripheral nerve ultrasound, and feature selection via artificial intelligence are facilitating more accurate diagnosis of axonal GBS. Nevertheless, some key issues, such as genetic susceptibilities, remain unanswered and moreover, current therapies bear limitations. Although several therapies have shown considerable benefits to experimental animals, randomized controlled trials are still needed to validate their efficacy.

Macrophage migration inhibitory factor (MIF) plays an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN), which may offer an opportunity for the development of the novel therapeutic strategies for GBS. Areas covered: 'macrophage migration inhibitory factor' and 'Guillain-Barré syndrome' were used as keywords to search for related publications on Pub-Med, National Center for Biotechnology Information (NCBI), USA. MIF is involved in the etiology of various inflammatory and autoimmune disorders. However, the roles of MIF in GBS and EAN have not been summarized in the publications we identified. Therefore, in this review, we described and analyzed the major roles of MIF in GBS/EAN. Primarily, this molecule aggravates the inflammatory responses in this disorder. However, multiple studies indicated a protective role of MIF in GBS. The potential of MIF as a therapeutic target in GBS has been recently demonstrated in experimental and clinical studies, although clinical trials have been unavailable to date. Expert opinion: MIF plays a critical role in the initiation and progression of GBS and EAN, and it may represent a potential therapeutic target for GBS.

Background It remains an urgent need for early recognition of disease severity, treatment option and outcome of Guillain-Barré syndrome (GBS). The chief complaint may be quickly obtained in clinic and is one of the candidates for early predictors. However, studies on the chief complaint are still lacking in GBS. The aim of the study is to describe the components of chief complaints of GBS patients, and to explore association between chief complaints and disease severity/treatment option/outcome of GBS, so as to aid the early prediction of the disease course and to assist the clinicians to prescribe an optimal early treatment. Methods A total of 523 GBS patients admitted to the First Hospital of Jilin University from 2003 to 2013 were enrolled for retrospective analysis. The data of chief complaints, clinical manifestations, and treatment options, etc. were collected. The clinical severity was evaluated by the Medical Research Council sum score and the Hughes Functional Grading Scale. The prognosis at 6 month after discharge was described by modified Erasmus GBS outcome score. The clinic GBS severity evaluation scale (CGSES), a newly established model in our study, was used to explore the role of chief complaints to predict intravenous immunoglobulin (IVIg). Results The major components of the chief complaints of GBS patients were weakness, numbness, pain, cranial nerve involvement, dyspnea, ataxia and autonomic dysfunction. Chief complaint of weakness was a predictor of severe disease course and poor short-term outcome, while chief complaint of numbness and cranial nerve involvement were promising predictors. Cranial nerve involvement was the predictor of ventilator dependence. The percentages of 366 GBS patients, who need IVIg treatment at nadir with CGSES ranging from 1 to 4, were 50.00, 67.34, 80.61, and 90.67%, respectively. Conclusions Chief complaints are clinic predictors of disease severity, ventilator dependence and short-term outcome. IVIg treatment during hospitalisation could be predicted in clinic using CGSES score.

// Ying Wang 1 , Wenjuan Lang 1 , Yaqian Zhang 1 , Xiaoyi Ma 2 , Chunkui Zhou 1 and Hong-Liang Zhang 1,3 1 Department of Neurology, The First Hospital of Jilin University, Changchun, China 2 Department of Neurology, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China 3 Department of Life Sciences, The National Natural Science Foundation of China, Beijing, China Correspondence to: Ying Wang, email: // Chunkui Zhou, email: // Hong-Liang Zhang, email: // Keywords : Guillain-Barre syndrome, long-term prognosis, predictors, self-limitation, intravenous immunoglobulin Received : July 12, 2017 Accepted : August 17, 2017 Published : September 01, 2017 Abstract Background: The long-term follow-up system for Guillain-Barre syndrome (GBS) is not well established worldwide. In our study, the preliminary data of the long-term prognosis of GBS are collected to explore the prognosis of GBS and the effect of intravenous immunoglobulin (IVIg) treatment. Methods: The follow-up data of 186 patients with GBS admitted from 2003 to 2013 were collected in 2015 via phone interview. The GBS disability scale score was ranked by clinician to evaluate the long-term prognosis. The clinical data during the acute phase were also collected. Results: The mortality rates were 2.15%, 5.45% and 7.89% at discharge, 2-5 years and 6-10 years after disease, respectively. The GBS disability scale score improved dramatically from discharge to 2-12 years after the acute phase. The self-limitation, the spontaneous recovery of disease, occurred both at acute phase and 2-5 years after discharge. Comparisons between IVIg-treated patients and GBS patients who only received supportive care revealed no significant difference of long-term prognosis. Conclusion: The long-term prognosis of GBS appears not to be influenced by treatment options. The long-term improvement of IVIg treated-patients might be due to the self-limitation of GBS per se instead of the IVIg treatment.

Background In the present study, we investigated the immuno-regulatory and therapeutic effects of Bowman–Birk inhibitor concentrate (BBIC) on experimental autoimmune neuritis (EAN), an animal model of Guillain–Barre syndrome (GBS) in human. Methods EAN in Lewis rats induced by inoculation with peripheral nerve myelin P0 protein peptide 180-199 (P0 peptide) was treated with BBIC at two different therapeutic regimens. Results Our data indicated that the administration of BBIC daily orally effectively inhibited and ameliorated the clinical and pathological signs of EAN. The suppression of EAN was associated with an insufficiency of autoreactive T cells, as reflected by inhibited P0 peptide-specific mononuclear cell proliferation and decreased in CD4 and CD8 T cells infiltrating into the peripheral nervous system (PNS). BBIC might mediate its therapeutic effects by shifting macrophages from M1 to M2 subtype as evidenced by increasing Arg-1, CD206 and IL-10 and inhibiting IFN-γ, TNF-α, IL-12, iNOS and CD40 expressions on macrophages as well as enhancing anti-inflammatory cytokines IL-4 and IL-10 and decreasing inflammatory cytokines, IFN-γ, TNF-α and IL-17 in the PNS. Conclusion Our results suggest that BBIC may have therapeutic potential in human GBS and other autoimmune diseases in the future.

Background We describe a case of Guillain-Barre syndrome (GBS) associated with hemorrhagic fever with renal syndrome. To our knowledge, only five cases of GBS associated with Hantavirus infection have been reported so far. Case presentations A 62-year-old man presented intermittent fever, chill and oliguria. According to remarkable leukocytosis, atypical lymphocytes, thrombocytopenia and former dwelling in hemorrhagic fever-endemic area, he was suspected as hemorrhagic fever with renal syndromeand certified with positive Hantavirus IgG. Later, the patient had symmetrical flaccid paralysis of all extremities. Electromyography showed peripheral nerve injury (mainly in axon). The patient was diagnosed as having acute motor sensory axonal neuropathy (AMSAN). After immunoglobulin infusion, patient showed progressive recovery and was transferred 3 weeks after his first admission to a rehabilitation center. Conclusions Our case was the 6th reported case of GBS associated with hemorrhagic fever with renal syndrome. Moreover, we for the first time classified the subtype of GBS (AMSAN) based on the electrophysiology characteristics. GBS should be suspected in patients who are already diagnosed as hemorrhagic fever with renal syndrome when delayed symmetrical limb paralysis occurs. Until recent now, GBS was only reported in hemorrhagic fever patients in Europe and Asia, which termed as hemorrhagic fever with renal syndrome.

The aim of this study was to determine the associations between serum folate level and the clinical course and severity of Guillain-Barré syndrome (GBS). We retrospectively enrolled 112 pairs of GBS patients and age- and sex-matched healthy controls with measured serum folate levels. On admission, 21 (18.9%) GBS patients had folate deficiency, of which only two were female patients. Patients with normal folate levels had a shorter disease progression than those with folate deficiency (median progression duration: 6 versus 13 days, p < 0.001). Serum folate levels on admission were correlated with progression duration and Medical Research Council (MRC) sum score in the upper limbs at nadir (r = -0.261, p = 0.005; r = -0.208, p = 0.03) but not with the duration of hospital stay or GBS disability score (p > 0.05). Logistic regression analysis revealed that normal folate levels on admission were an independent predictor of faster GBS progression, along with younger age, intact deep sensation, and a lower MRC sum score on admission. These results show that serum folate levels are correlated with the progression duration and severity of GBS. Further studies are required to confirm the potential of folate level as a biomarker for GBS prognosis.

Guillain-Barré syndrome (GBS) is an immune-mediated acute inflammatory disorder of the PNS in humans characterized by inflammatory infiltration and damage to myelin and axon. Experimental autoimmune neuritis (EAN) is a useful animal model for studying the pathogenesis and treatment of GBS. Immunocompetent cells together with cytokines produced by various cells contribute to the inflammatory process of GBS and EAN by acting as mediators or effectors.Both GBS and EAN have long been attributed to T helper (Th) 1 cell-mediated autoimmune disorders. IFN-γ acts as a central mediator of Th1-mediated autoimmune disorders by deflecting the immune response toward a Th1 phenotype by inducing the differentiation of T cells to a Th1 phenotype and inhibiting the development of Th2 cells in autoimmune disorders such as GBS. In this review, we present an overview of current knowledge on the inflammatory and immunoregulatory role of IFN-γ in GBS and EAN, which is important for evaluating whether IFN-γ can become a potential therapeutic target in GBS.Analysis of immunopathogenesis of GBS and EAN revealed the significance of IFN-γ in both diseases, even though the complex mechanism of the delicate modulation of the cytokine is still under debate. More work needs to be done to rule out its potential in immunoregulatory function and pave the way for new therapeutic strategies for GBS.

The Guillain-Barré syndrome (GBS) is considered a T helper 1 (Th1) cells-mediated acute inflammatory peripheral neuropathy. However, some changes in GBS could not be explained completely by Th1 cells pathogenic role. Recently, Th17 cells have been identified and can mediate tissue inflammation and autoimmune response. Therefore, a study on the role of Th17 and Th22 cells and their cytokines in GBS is necessary for exploring the pathogenesis of GBS. Here, we detected the frequency of Th1, Th17, and Th22 cells by using 4-color flow cytometry and we detected the plasma levels of IL-17 and IL-22 by ELISA in GBS patients, relapsing-remitting multiple sclerosis patients at the acute phase of relapse, viral encephalitis or meningitis patients and healthy controls. Our data showed that the frequency of circulating Th1, Th17, and Th22 cells was significantly increased in GBS patients. The plasma levels of IL-17 and IL-22 in GBS and relapsing-remitting multiple sclerosis at the acute phase of relapse were also markedly elevated. Enhanced circulating Th22 cells were correlated with GBS severity. Intravenous immunoglobulin therapy downregulated Th17, and Th22 cells and the plasma levels of IL-17 and IL-22 in GBS patients. Th17 and Th22 cells may be involved in the pathogenesis of GBS, and intravenous immunoglobulin mediates therapeutic effects by downregulating these cells and their cytokines.

Introduction: Guillain-Barre syndrome (GBS) is an immune-mediated disorder in the peripheral nervous system (PNS), and experimental autoimmune neuritis (EAN) serves as an animal model of GBS. TNF-α plays an important role in the pathogenesis of GBS and is a potential therapeutic target of GBS.Areas covered: ‘TNF-α’ and ‘Guillain-Barre syndrome’ were the keywords used to search for related publications on Pubmed. By binding to different TNF receptors, TNF-α bears distinct immune properties. TNF-α gene polymorphisms are associated with the features of GBS. The major role of TNF-α in GBS/EAN is to aggravate inflammation; however, data from several studies indicated a protective role of TNF-α. Multiple lines of evidence point to TNF-α as a potential therapeutic target for GBS. However, such clinical trials are scarce in that GBS per se is a probable side effect of anti-TNF-α treatment.Expert opinion: TNF-α plays a dual role in GBS and EAN, and is a potential therapeutic target on GBS/EAN.

Objective Clinical characteristics of pediatric Guillain-Barré syndrome (GBS) have been extensively studied whereas scarcely been compared with those of adult GBS. Herein we compared the clinical features of GBS between pediatric and adult patients. Methods We retrospectively collected the clinical data of 750 patients with GBS (541 adults and 209 children), and compared the clinical characteristics between children and adults. Results Pain was a more frequent complaint in children (17.2% vs 9.6%, p < 0.01), who were also found with shorter interval from disease onset to nadir (6.3d vs 7.3d, p < 0.01) and higher incidence of bulbar dysfunction (22.0% vs 14.8%, p < 0.05). The disease severity in children was comparable with adults. In addition, a higher incidence of pediatric GBS was found in summer, especially in July and August (both p < 0.01). However, the incidence of antecedent infections of different seasons in adult and pediatric patients was comparable (p > 0.05). The clinical features of acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) in children were overall comparable with adult ones (p > 0.05). Similar to adults, bulbar dysfunction (odds ratio [OR]: 4.621, 95% confidence interval [CI]: 1.240–17.218, p < 0.05) and lower nadir Medical Research Council (MRC) sum score (OR: 0.897, 95% CI: 0.855–0.941, p < 0.01) were also risk factors for mechanical ventilation in children. However, distinct from adult ones, autonomic dysfunction was significantly higher in mechanically ventilated childhood GBS (39.1% vs 8.8%, p < 0.01), which also served as a predictor for mechanical ventilation in pediatric GBS (OR: 70.415, 95% CI: 9.265–535.158, p < 0.01). As to the efficacy of intravenous immunoglobulin, insignificant difference was identified between children and adults. Conclusion The clinical features of pediatric GBS differ from those of adults. Autonomic dysfunction is an independent risk factor for mechanical ventilation in pediatric patients.

Macrophages are important immune cells of the innate immune system that are involved in organ-specific homeostasis and contribute to both pathology and resolution of diseases including infections, cancer, obesity, atherosclerosis, and autoimmune disorders. Multiple lines of evidence point to macrophages as a remarkably heterogeneous cell type. Different phenotypes of macrophages exert either proinflammatory or anti-inflammatory roles depending on the cytokines and other mediators that they are exposed to in the local microenvironment. Proinflammatory macrophages secrete detrimental molecules to induce disease development, while anti-inflammatory macrophages produce beneficial mediators to promote disease recovery. The conversion of the phenotypes of macrophages can regulate the initiation, development, and recovery of autoimmune diseases. Human neuroimmune diseases majorly include multiple sclerosis (MS), neuromyelitis optica (NMO), myasthenia gravis (MG), and Guillain-Barré syndrome (GBS) and macrophages contribute to the pathogenesis of these neuroimmune diseases. In this review, we summarize the double roles of macrophage in neuroimmune diseases and their animal models to further explore the mechanisms of macrophages involved in the pathogenesis of these disorders, which may provide a potential therapeutic approach for these disorders in the future.

Guillain-Barré syndrome (GBS) is an immune-mediated inflammatory disease in the peripheral nervous system. Specific biomarkers for the two most common clinical subtypes of GBS, i.e., acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) are still missing. The distinctive pathological features of AIDP and AMAN may lead to release of such specific biomarkers including glial markers (calcium-binding astroglial protein, S100B) and axonal damage markers [axoskeletal protein, phosphorylated neurofilament heavy protein (pNFH); cytoskeletal protein, tau], etc. To explore the potentials of biochemical markers for differential diagnosis and evaluation of prognosis of clinical subtypes in GBS, we used ELISA to measure the levels of S100B, tau and pNFH in serum and cerebrospinal fluid (CSF) from the patients with AIDP, AMAN, viral encephalitis and other non-inflammatory neurological disorders (OND), respectively. The values of albumin quotient and IgG index in CSF are significantly higher in AIDP and AMAN than in OND. The levels of S100B, tau and pNFH in serum and CSF are elevated in the patients with AIDP and AMAN compared to OND. The concentrations of these proteins are all higher in CSF than in serum. Increased levels of S100B in CSF at the acute phase are positively correlated with the GBS disability scale scores (GDSs) in AIDP, whereas enhanced levels of tau and pNFH in CSF are positively correlated with the GDSs in AMAN. Increased CSF levels of S100B, tau and pNFH at the acute phase may predict a poor prognosis and evaluate the severity of AIDP or AMAN at plateau and the recovery phase. Elevated levels of pNFH in CSF may be used for differentiating between AMAN and AIDP.

Zhang H-L, Zhang X-M, Mao X-J, Deng H, Li H-F, Press R, Fredrikson S, Zhu J. Altered cerebrospinal fluid index of prealbumin, fibrinogen, and haptoglobin in patients with Guillain–Barre syndrome and chronic inflammatory demyelinating polyneuropathy. Acta Neurol Scand: 2012: 125: 129–135. © 2011 John Wiley & Sons A/S. Objectives – Guillain–Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are autoimmune diseases of the peripheral nervous system. A clinical hallmark of GBS and CIDP is the albumino-cytologic dissociation in the cerebrospinal fluid (CSF). Changes in the CSF levels of proteins other than albumin in patients with GBS and CIDP are not as well studied. If altered, aberrant levels of CSF proteins may render it possible to establish useful biomarkers for GBS and CIDP. Materials and methods – Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of prealbumin, fibrinogen, haptoglobin, apolipoprotein E, apolipoprotein A4 in both CSF and plasma samples from 19 patients with GBS and eight with CIDP, 24 controls with multiple sclerosis (MS) as well as 20 patients with other non-inflammatory neurological disorders (OND). Results – The levels of prealbumin in both the plasma and the CSF were elevated in patients with GBS and MS compared with the controls. The higher levels of fibrinogen were seen in the CSF of patients with GBS and CIDP, but not in the plasma. The levels of CSF prealbumin and fibrinogen, measured by the CSF index of these proteins, were lower in patients with GBS and that of fibrinogen in patients with CIDP compared with controls with OND. Haptoglobin levels in the CSF rather than in the plasma were higher in patients with GBS and CIDP than in controls. The CSF haptoglobin index was higher in patients with CIDP and MS, but not in those with GBS. No correlation was found between levels of CSF proteins and clinical parameters in patients with GBS and CIDP. Conclusions – Our data provide preliminary evidence that GBS is associated with low CSF index levels of prealbumin and fibrinogen, but normal levels of haptoglobin, whereas CIDP is associated with normal CSF index levels of prealbumin, low fibrinogen, and high levels of haptoglobin. Further studies are needed to identify the underlying mechanisms behind these CSF protein alterations and to clarify whether prealbumin, fibrinogen, and haptoglobin can serve as useful biomarkers for GBS and CIDP.

Guillain-Barré syndrome (GBS) is an immune-mediated inflammatory disorder of the peripheral nervous system (PNS). Experimental autoimmune neuritis (EAN) is a useful animal model for studying GBS. Currently, GBS remains a life-threatening disorder and more effective therapeutic strategies are in urgent need.Accumulating evidence has revealed that T helper (Th) 17 cells and their cytokines are pathogenic in GBS/EAN. Drugs attenuated clinical signs of GBS/EAN, in part, by decreasing Th17 cells or IL-17A. Th17 cells and their cytokines might be potential therapeutic targets. Approaches targeting Th17 cells or their cytokines are in development in treating Th17 cells-involved disorders. In this review, we summarize the up-to-date knowledge on roles of Th17 cells and their cytokines in GBS/EAN, as well potential approaches targeting Th17 cells and their cytokines as clinical applications.As Th17 cells produce different sets of pro-inflammatory cytokines and Th17-related cytokines are not exclusively produced by Th17 cells, targeting Th17 cell development may be superior to blocking a single Th17 cytokine to treat Th17 cells-involved disorders. Considering the essential role of retinoic acid-related orphan receptor γT (RORγT) and IL-23 in Th17 cell development, RORγT inhibitors or IL-23 antagonists may provide better clinical efficacy in treating GBS/EAN.

Guillain-Barré syndrome (GBS), the axonal subtype of which is mainly triggered byC. jejuniwith ganglioside-mimicking lipooligosaccharides (LOS), is an immune-mediated disorder in the peripheral nervous system (PNS) accompanied by the disruption of the blood-nerve barrier (BNB) and the blood-cerebrospinal fluid barrier (B-CSF-B). Biomarkers of GBS have been extensively explored and some of them are proved to assist in the clinical diagnosis and in monitoring disease progression as well as in assessing the efficacy of immunotherapy. Herein, we systemically review the literature on biomarkers of GBS, including infection-/immune-/BNB, B-CSF-B, and PNS damage-associated biomarkers, aiming at providing an overview of GBS biomarkers and guiding further investigations. Furthermore, we point out further directions for studies on GBS biomarkers.

Introduction Guillain-Barré syndrome (GBS) is an immune-mediated disorder of the peripheral nervous system. Respiratory failure requiring mechanical ventilation (MV) is a serious complication of GBS. Identification of modifiable risk factors for MV and poor short-term prognosis in mechanically ventilated patients with GBS may contribute to the individualized management and may help improve the outcome of the patients. Methods We retrospectively analyzed the clinical data of 541 patients who were diagnosed with GBS from 2003 to 2014. Independent predictors for MV and short-term prognosis in mechanically ventilated patients were identified via multivariate logistic regression analysis. Results The mean age was 41.6 years with a male predilection (61.2 %). Eighty patients (14.8 %) required MV. Multivariate analysis revealed that shorter interval from onset to admission (p p p p p p p p Conclusions Clinical predictors of MV and poor short-term prognosis in mechanically ventilated GBS patients were distinct. Add-on use of intravenous corticosteroids was a risk factor for poor short-term prognosis in mechanically ventilated patients with a nadir MRC sum score from 0 to 12 points.

Objective A potential association between diabetes and Guillain-Barré syndrome (GBS) has been indicated by a few case studies. We retrospectively analyzed the clinical features of a large cohort of GBS patients to explore the relationship between the level of fasting plasma glucose (FPG) obtained in the acute phase at admission and the severity of GBS. Methods Three hundred and four GBS patients were divided into two groups, one with normal FPG and the other with high FPG levels according to the international standards of FPG. Results The GBS disability scale score was positively, the Medical Research Council (MRC) sum score was negatively correlated to the level of FPG, but not to blood HBA1c or CSF glucose concentrations. A relatively higher FPG level was observed in older and younger GBS patients, and more often in those with cranial nerve involvement, autonomic deficit, dyspnea and ventilator dependence than in patients without these clinical characteristics. Importantly, higher levels of FPG at admission were associated with poorer short-term prognosis measured by the MRC sum score and the GBS disability scale at discharge. Conclusions Our data demonstrates that FPG in the acute phase of GBS correlates with the severity of GBS and may predict the short-term prognosis of GBS.

To investigate the clinical characteristics and short-term prognosis of elderly patients with Guillain–Barré syndrome (GBS). We retrospectively analyzed the clinical data of adult GBS. According to the age, the enrolled subjects were divided into 2 groups, that is, patients ≥60 years (elderly group) and those aged 18 to 59 years (nonelderly group). The clinical characteristics and short-term prognosis of the patients in the 2 groups were compared. In total, 535 patients were enrolled. There were 67 patients fell into the elderly group with a mean age of 69 years old; while 468 patients fell into the nonelderly group with a mean age of 39 years old. We found that the elderly patients had significantly lower incidence of antecedent infections (49.3% vs 66.2%, P

Experimental autoimmune neuritis (EAN), an animal model of human Guillain-Barre syndrome, has long been considered as a T helper (Th) 1 cell-mediated autoimmune disorder. However, deficiency of IFN-γ, a signature Th1 cytokine, aggravated EAN, with features of elevated production of IL-17A, despite an alleviated systemic Th1 immune response. We hypothesized that Th17 cells and their cytokines might play a pathogenic role in EAN. To further clarify the roles of these Th and regulatory T cell (Treg) cytokines in the pathogenesis of EAN and their interrelationship, we investigated the expression of Th1/Th2/Th17/Treg cytokines in EAN in this study. We found that the levels of Th17 cells and IL-17A in cauda equina (CE)-infiltrating cells and splenic mononuclear cells (MNCs) as well as in serum paralleled the disease evolution, which increased progressively during the initiation stage and reached higher value at the peak of EAN. The same pattern was also noticed for the expression of IL-22. The diverse expression profiles of FoxP3, IL-17 receptors A and C were seen in CE-infiltrating cells and splenic MNCs in EAN. These findings indicate a major pro-inflammatory role of Th17 cells and IL-17A in the pathogenesis of EAN. Therapeutic interventions may be focused upon inhibiting Th17 cells and their cytokines in the early phase of EAN, so as to delay and suppress clinical signs of the disease, which has relevance for future studies on pathogenesis and treatment of GBS in humans.

Guillain–Barre syndrome (GBS) is an immune-mediated acute inflammatory disorder in the peripheral nervous system (PNS) of humans characterized by inflammatory infiltration and damage to myelin and axon. Experimental autoimmune neuritis (EAN) is a useful animal model for GBS. Although GBS and EAN have been widely studied, the pathophysiological basis of GBS/EAN remains largely unknown. Immunocompetent cells together with cytokines produced by various cells contribute to the inflammatory process of EAN by acting as mediators or effectors. Both GBS and EAN have hitherto been attributed to T helper (Th)1 cells-mediated disorders, however, some changes in GBS and EAN could not be explained by the pathogenic role of Th1 cells and a disturbance of the Th1/Th2 balance, which has previously been considered to be important for the homeostatic maintenance of the immune responses and to explain the adaptive immunity and autoimmune diseases. The Th1/Th2 paradigm in autoimmune diseases has been greatly challenged in recent years, with the identification of a particular T cell subset Th17 cells. Studies on the associations between Th17 cells/cytokines and GBS/EAN are reviewed. But some of them occasionally yield conflicting results, indicating an intricate network of cytokines in immune response.

Guillain-Barré syndrome (GBS) is an acute autoimmune-mediated inflammatory demyelinating disease that causes rapidly progressing paralysis and occasionally respiratory failure. We hypothesized that interleukin (IL)-17 and IL-22 are elevated in GBS and participate in the autoimmune inflammatory response of GBS. We used sandwich enzyme-linked immunosorbent assay (ELISA) to measure the IL-17 and IL-22 levels in the CSF, and plasma from 22 GBS patients at the acute phase and 18 healthy controls (HC). The results show that CSF and plasma levels of IL-17 and IL-22 are elevated in GBS patients compared with HC. IL-17 and IL-22 levels in CSF, respectively, are correlated with GBS disability scale scores (GDSs). Meanwhile, IL-17 and IL-22 levels in CSF, IL-22 in CSF, and plasma of GBS patients have positive correlation, respectively. The increased levels of IL-17 and IL-22 in CSF may be explained by the disruption of blood-brain barrier (BBB) and peripheral nervous system (PNS) local inflammation in GBS. Meanwhile, the elevated levels of these two cytokines in plasma suggest the activation of Th17 and Th22 cells in the systemic immune response of GBS. Our data provide preliminary evidence that GBS is associated with high levels of IL-17 and IL-22 in CSF and plasma. These cytokines display pathogenic potential and may serve as useful biomarkers for GBS.

We read the case report with great interest by Song et al. [1]. The reported case was diagnosed as acute motor axonal neuropathy, a variant of Guillain–Barre syndrome (GBS) based on the clinical symptoms and laboratory and electrophysiological results. Nevertheless, the case may be misdiagnosed, since there are the overlaped evidences of other diseases, which are the same with onset histories, physical examinations, the laboratory and electrophysiological results, etc. Although these evidences have been leveled at various aspects of GBS diagnosis, nowadays the pathological and immunological proofs, for instance, the muscle and nerve biopsy as well as humoral antibodies analysis have almost been supportively used in excluding these diseases with some identical characteristics from the neuromuscular spectrum for clinical diagnosis. There are two kinds of neuromuscular abnormalities in ICU. The first kind refers to the neuromuscular disease such as GBS in ICU. Another one, flaccid paralysis without preexisting neuromuscular disorders is acquired in ICU like critical illness polyneuropathy (CIP) and/or critical illness myopathy (CIM). GBS is often hard to be differentiated with CIP/CIM, especially an axonal damage form of GBS may be more difficult to distinguish from CIP due to the similar electromyography signs. Generally, CIP or CIM should be the foremost suspected disorder after sepsis, after all, the most likely cause of limb muscle weakness in ICU is CIP/CIM [2], because *70% of the patients with sepsis or systemic inflammatory response syndrome [3], and up to 100% of the patients with multiple organ failure (MOF) developed CIP and/or CIM [4]. CIP and CIM prolong weaning from mechanical ventilation and physical rehabilitation. Making an accurate diagnosis for GBS will be lying on the full analysis of clinical, laboratory and electrophysiological data, and the adequate experience from the clinician. Although detailed history, careful physical examinations, routine laboratory studies, and electrophysiological investigations might be very useful in the common patients, the muscle and nerve biopsy could give supportive discrimination between CIP/CIM and GBS, after the patients suffering from sepsis or MOF. Albuminocytological dissociation in the cerebrospinal fluid (CSF) is the highly specialized characteristic of GBS; however, the clinician still needs to consider that non-immunological factors can also increase the protein levels in CSF, i.e. fake albumino-dissociation phenomenon. As a matter of fact, not only hemorrhagic stroke rupturing into the fourth ventricle like this case can cause the protein levels to enhance in CSF, but also even the reduplicative lumbar punctures can also result in the ascending of the protein levels in CSF. So, it is necessary to prove the myosin depletion in the muscle fibers through a biopsy in CIM [5], X.-K. Wang J. Zhu Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China

Intravenous immunoglobulin (IVIg) has been proven most effective in treating Guillain–Barré syndrome (GBS). Corticosteroids as an add-on therapy have been prescribed in severe GBS cases. However, the efficacy of intravenous corticosteroids combined with IVIg in dealing with severe GBS remains unclear. We explored the therapeutic effects of different therapeutic regimens on the short-term prognosis of GBS patients, especially the severe cases. We retrospectively analyzed the clinical data of 527 adult patients with GBS who were prescribed to different treatments from 2003 to 2014. The therapeutic effect of a treatment was evaluated by the improvement of Hughes Functional Grading Scale (HFGS) and Medical Research Council (MRC) sum score. With comparable incidence of infectious complications (P > 0.05), more mechanically ventilated patients were found improvement after IVIg treatment than combination IVIg with intravenous corticosteroids (MRC: 97% vs. 72.4%, P 0.05) and ratio of patients who were improved after IVIg were insignificantly different from the combination therapy (MRC: 89.6% vs. 86.5%; HFGS: 69.6% vs. 61.5%; both P > 0.05), even if the intravenous corticosteroids were initiated within 7 days after onset (P > 0.05). In addition, supportive treatment was sufficient for patients who were able to walk with help (HFGS = 3) and mildly affected (HFGS 3), while corticosteroids are detrimental for short-term prognosis in mechanically ventilated patients when used in combination with IVIg. Further prospective and randomized studies are warranted to validate this finding.