Pathogenesis Of Guillain-Barré Syndrome Research Articles

Heterotopic ossification Post-Guillain barre syndrome in Saudi Arabia: a case report

Background: Heterotopic ossification (HO) is the formation of bone within the soft tissues. It can be a complication of Guillain-Barre syndrome (GBS). There are many risk factors for HO, including male sex, mechanical ventilation, and neurogenic trauma. Myelin and axons are the main targets and areas of injury in GBS, an autoimmune-inflammatory neuropathy. Literatures shows that this may possibly be associated with the initial administration of the coronavirus (COVID)-19 vaccine and GBS. Presentation of the case: A 27-year-old male was diagnosed with bile reflux gastritis. Days later, he presented to the emergency room (ER) with progressive weakness and a critical condition that required intensive care unit admission (ICU). The patient undergoes intubation and remains in the ICU for four months. The patient, after extensive rehabilitation, started to complain of left hip pain and limitations of motion. Radiographs confirmed the HO diagnosis. Past drug history showed patients received a single dose of the COVID-19 vaccine 15 days before presentation to the ER. Discussion: There is no clear association between the COVID-19 vaccination and GBS. HO is formation of abnormal bone within soft tissue. HO post-GBS usually affects large joints like the hips, knees, and shoulders. Researchers poorly understand the pathogenesis of GBS. Conclusion: Despite the absence of a definitive correlation between GSB and the COVID-19 vaccine. Physicians should maintain a state of suspicion while treating patients with a progressive weakness. Additional research is required.

Guillain-Barre syndrome and link with COVID-19 infection and vaccination: a review of literature.

Guillain-Barré syndrome (GBS) is an autoimmune disease associated with significant morbidity. A wide variety of infectious and non-infectious triggers have been identified to be associated with GBS. COVID-19 has gained attention in recent years for its role in GBS pathogenesis. Our study aims to review the literature on GBS and its epidemiological and pathophysiological association with COVID-19. Recent literature on GBS associated with COVID-19 infections, such as case reports, case series, systematic reviews, and large-scale epidemiological studies, were reviewed. We also reviewed studies that included vaccines against COVID-19 in association with GBS. Studies that focused on understanding the pathobiology of GBS and its association with infectious agents including COVID-19 were reviewed. Despite a lack of consensus, GBS is strongly associated with COVID-19 infection. The exact pathophysiological mechanism regarding COVID-19 as a causative agent of GBS is unknown. Mechanisms, such as the proinflammatory state, triggering of autoimmunity, and direct viral invasion, are postulated and remain to be investigated. Adenovirus vector vaccines are most likely associated with GBS, and the consensual reports clearly suggest mRNA vaccines are associated with low risk and may be protective against GBS by reducing the risk of COVID-19 infection.

Guillain-Barré syndrome

Guillain-Barré syndrome (GBS), an acute immune-mediated neuropathy, occurs following immunological stimulation, such as infection, with complement-mediated neuropathy implicated in the pathophysiology of this condition. Glycolipid antibodies produced by molecular mimicry are detected in approximately 60% of cases. Recent studies have suggested the role of cell-mediated immunity in the pathogenesis of GBS. Intravenous immunoglobulin and plasma exchange are established immunotherapies. In this article, based on the latest knowledge, we describe the pathophysiology, diagnosis, treatment, prognosis, and prognostic prediction of GBS. Furthermore, we discuss some GBS guidelines published by the European Academy of Neurology/Peripheral Nerve Society.

Extensive cytokine biomarker analysis in serum of Guillain-Barré syndrome patients

Guillain-Barré syndrome (GBS) is an acute idiopathic polyneuropathy which is related to infection and immune mechanism. The exact pathogenesis of the disease is unknown and treatment is limited. Thus, the purpose of the study is to identify biomarkers of GBS serum and elucidate their involvement in the underlying pathogenesis of GBS that could help to treat GBS more accurately. Antibody array technology was used to detect the expression levels of 440 proteins in serum of 5 GBS group and 5 healthy control group. Sixty-seven differentially expressed proteins (DEPs) were identified by antibody array, among which FoLR1, Legumain, ErbB4, IL-1α, MIP-1α and IGF-2 were down-regulated, while 61 proteins were up-regulated. Bioinformatics analysis indicated that most DEPs were associated with leukocytes, among which IL-1α, SDF-1b, B7-1, CD40, CTLA4, IL-9, MIP-1α and CD40L were in the center of protein–protein interaction (PPI) network. Subsequently, the ability of these DEPs to distinguish GBS from healthy control was further evaluated. CD23 was identified by means of Random Forests Analysis (RFA) and verified by enzyme-linked immunosorbent assay (ELISA). The ROC curve result of CD23 respectively displayed that its sensitivity, specificity and AUC were 0.818, 0.800 and 0.824. We speculate that activation of leukocyte proliferation and migration in circulating blood might be associated with inflammatory recruitment of peripheral nerves, leading to the occurrence and development of GBS, but this conclusion still requires deeper confirmation. More importantly, central proteins may play a pivotal role in the pathogenesis of GBS. In addition, we detected IL-1α, IL-9, and CD23 in the serum of GBS patients for the first time, which may be promising biomarkers for the treatment of GBS.

Guillain-Barré Syndrome Induced by Vaccination Against COVID-19: A Systematic Review and Meta-Analysis.

Guillain-Barré syndrome (GBS) is a rare but serious immune-mediated neurological condition characterized by damage to the peripheral nervous system.Two-thirds of cases of GBS are diagnosed following infection; however, vaccination has also been linked to GBS pathogenesis. The aim of this systematic review and meta-analysis was to establish the prevalence of GBS following vaccination against the SARS-CoV-2 virus, which causes COVID-19, describe the clinical and neurophysiological characteristics, and identify potential determinants. A systematic review of the literature regarding post-vaccination GBS was conducted using the PubMed database. Seventy papers were included. The pooled prevalence of GBS after vaccination against COVID-19 per has been established to be 8.1 (95% CI 30-220) per 1,000,000 vaccinations. Vaccination with vector vaccines - but not mRNA - has been associated with an increased risk of GBS. More than 80% of the patients developed GBS within 21 days following the first dose of the vaccination. The interval between the vaccination and GBS was shorter in patients who were vaccinated with mRNA versus vector vaccines (9.7±6.7 days versus 14.2±6.6 days). Epidemiological findings regarding post-vaccination GBS revealed a higher prevalence in males and people between the ages of 40 and 60 years, with a mean age of 56.8±16.1 years. The most common type was the acute inflammatory demyelinating polyneuropathy type. Most cases responded well to treatment. In conclusion, vaccination against COVID-19 with vector vaccines seems to increase the risk of GBS. GBS occurring following vaccination does differ in characteristics from GBS during the pre-COVID-19 era.

Deciphering the Role of Schwann Cells in Inflammatory Peripheral Neuropathies Post Alphavirus Infection

Old world alphaviruses (e.g., chikungunya) are known to cause severe acute and chronic debilitating arthralgia/arthritis. However, atypical neurological manifestations and, in particular, unexpected cases of acute inflammatory Guillain-Barre syndrome (GBS) have been associated with the arthritogenic alphaviruses. The pathogenesis of alphavirus-associated GBS remains unclear. We herein addressed for the first time the role of Schwann cells (SC) in peripheral neuropathy post-alphaviral infection using the prototypical ONNV alphavirus model. We demonstrated that human SC expressed the recently identified alphavirus receptor MxRA8 and granting viral entry and robust replication. A canonical innate immune response was engaged by ONNV-infected SC with elevated gene expression for RIG-I, MDA5, IFN-β, and ISG15 and inflammatory chemokine CCL5. Transcription levels of prostaglandin E2-metabolizing enzymes including cPLA2α, COX-2, and mPGES-1 were also upregulated in ONNV-infected SC. Counterintuitively, we found that ONNV failed to affect SC regenerative properties as indicated by elevated expression of the pro-myelinating genes MPZ and MBP1 as well as the major pro-myelin transcription factor Egr2. While ONNV infection led to decreased expression of CD55 and CD59, essential to control complement bystander cytotoxicity, it increased TRAIL expression, a major pro-apoptotic T cell signal. Anti-apoptotic Bcl2 transcription levels were also increased in infected SC. Hence, our study provides new insights regarding the remarkable immunomodulatory role of SC of potential importance in the pathogenesis of GBS following alphavirus infection.

Sex differences in Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy and experimental autoimmune neuritis.

Guillain Barré syndrome (GBS) and its variants, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP and its variants, are regarded as immune mediated neuropathies. Unlike in many autoimmune disorders, GBS and CIDP are more common in males than females. Sex is not a clear predictor of outcome. Experimental autoimmune neuritis (EAN) is an animal model of these diseases, but there are no studies of the effects of sex in EAN. The pathogenesis of GBS and CIDP involves immune response to non-protein antigens, antigen presentation through non-conventional T cells and, in CIDP with nodopathy, IgG4 antibody responses to antigens. There are some reported sex differences in some of these elements of the immune system and we speculate that these sex differences could contribute to the male predominance of these diseases, and suggest that sex differences in peripheral nerves is a topic worthy of further study.

Serum C3 complement levels predict prognosis and monitor disease activity in Guillain-Barré syndrome

ObjectiveBiomarkers are needed to predict prognosis and disease activity in patients with Guillain-Barré syndrome (GBS). The complement system is a key player in the pathogenesis of GBS. This study aimed to assess the potential utility of serum complement proteins as novel biomarkers in GBS. MethodsWe reviewed the medical records of 76 GBS patients with C3 and C4 measurements during hospitalization between 2010 and 2021. Clinical outcomes were correlated with baseline serum C3, C4, and seven additional predictors: four existing biomarkers (GM1, albumin, immunoglobulin G, neutrophil-lymphocyte ratio) and three clinical factors from the modified Erasmus GBS outcome score model. Five complement activation products (C3a, C4a, C5a, soluble C5b-9, factor Bb) were measured in 35 patients and were compared with C3 and C4 levels. Longitudinal changes in C3 and C4 levels were compared with the disease course in 12 patients. ResultsHigher C3, but not C4, was associated with poorer outcomes: lower Medical Research Council sum scores (MRCSS), higher GBS disability score (GBSDS), longer hospitalization, and more frequent treatment-related fluctuations. Age, MRCSS at admission, and baseline serum C3 were significant independent indicators of 1- and 3-month GBSDS. We found that C3 was positively correlated with C3a (r = 0.32) and C5a (r = 0.37), which indicates an activated complement cascade with high C3. Longitudinal change of C3 coincided with clinical severity of the disease course. InterpretationThis study highlights the use of serum C3 as a novel mechanistic biomarker in GBS. Larger prospective studies are needed to validate our findings.

Guillain-Barré syndrome in an era of global infections and 21st century vaccination.

Guillain-Barre syndrome is sometimes a severe and disabling postinfectious neuromuscular paralysis that is causally associated with a number of well defined infections, and occasionally with immunization. The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) pandemic and the worldwide immunization programme provoked fears of an epidemic of coronavirus disease 2019 (COVID-19) related disease. As we emerge from the pandemic this review summarises some of the huge volume of publications about Guillain-Barre syndrome (GBS), COVID-19 and immunisation against it. In the early months of COVID-19, there were concerns of significant numbers of cases of GBS resulting from SARS-CoV-2 infection. Large epidemiological studies have provided reassurance that the association of GBS with COVID-19 is small or absent. Despite considerable efforts, plausible pathogenic mechanisms aligned with our understanding of GBS causation have not been identified. Reliable data from national surveillance of COVID-19 vaccinations have shown GBS to occur at about 5.8 cases per million first doses of adenovirus vectored COVID-19 vaccines, otherwise not distinguishable from incident naturally occurring cases. However, this risk is far outweighed by the protective benefits of vaccination in the at-risk older deciles of age. With no obvious link of GBS to COVID-19 epitopes, in particular the spike (S-)protein, but a clearly demonstrable causation in some susceptible individuals from the global rollout of novel adenovirus vectored vaccine technologies, adenoviruses are of significant interest in the pathogenesis of GBS as well as vectors in their many expanding pharmaceutical applications.

Th1/Th17-mediated Immunity and Protection from Peripheral Neuropathy in Wildtype and IL10-/- BALB/c Mice Infected with a Guillain-Barré Syndrome-associated Campylobacter jejuni Strain.

Campylobacter jejuni is an important cause of bacterial gastroenteritis worldwide and is linked to Guillain-Barré syndrome (GBS), a debilitating postinfectious polyneuropathy. The immunopathogenesis of GBS involves the generation of antibodies that are cross reactive to C. jejuni lipooligosaccharide and structurally similar peripheral nerve gangliosides. Both the C. jejuni infecting strain and host factors contribute to GBS development. GBS pathogenesis is associated with Th2-mediated responses in patients. Moreover, induction of IgG1 antiganglioside antibodies in association with colonic Th2-mediated immune responses has been reported in C. jejuni-infected C57BL/6 IL10-/- mice at 4 to 6 wk after infection. We hypothesized that, due to their Th2 immunologic bias, BALB/c mice would develop autoantibodies and signs of peripheral neuropathy after infection with a GBS patient-derived strain of C. jejuni (strain 260.94). WT and IL10-/- BALB/c mice were orally inoculated with C. jejuni 260.94, phenotyped weekly for neurologic deficits, and euthanized after 5 wk. Immune responses were assessed as C. jejuni-specific and antiganglioside antibodies in plasma and cytokine production and histologic lesions in the proximal colon. Peripheral nerve lesions were assessed in dorsal root ganglia and their afferent nerve fibers by scoring immunohistochemically labeled macrophages through morphometry. C. jejuni 260.94 stably colonized both WT and IL10-/- mice and induced systemic Th1/Th17-mediated immune responses with significant increases in C. jejuni-specific IgG2a, IgG2b, and IgG3 plasma antibodies. However, C. jejuni 260.94 did not induce IgG1 antiganglioside antibodies, colitis, or neurologic deficits or peripheral nerve lesions in WT or IL10-/- mice. Both WT and IL10-/- BALB/c mice showed relative protection from development of Th2-mediated immunity and antiganglioside antibodies as compared with C57BL/6 IL10-/- mice. Therefore, BALB/c mice infected with C. jejuni 260.94 are not an effective disease model but provide the opportunity to study the role of immune mechanisms and host genetic background in the susceptibility to post infectious GBS.

Collaborative studies of U.S.-China neurologists on acute motor axonal neuropathy.

Collaborative studies of U.S.-China neurologists on acute motor axonal neuropathy.

Синдром Гійєна — ​Барре при запальних захворюваннях суглобів

Актуальність. Синдром Гійена — Барре (СГБ) при запальних хворобах суглобів описується у вигляді поодиноких спостережень, і багато клініко-патогенетичних аспектів такої периферійної нейропатії (ПНП) залишаються нез’ясованими. Мета дослідження: оцінити частоту й характер перебігу СГБ при ревматоїдному артриті (РА), реактивному хламідійному урогенітальному артриті (РеА), псоріатичному артриті (ПА) та анкілозуючому спондиліті (АС), вивчити патогенетичні побудови цієї нейропатії, виділити чинники ризику. Матеріал і методи. Під спостереженням перебували 416 пацієнтів із запальними захворюваннями суглобів, серед яких був 131 хворий на РА, 101 — на РеА, 76 — на ПА і 108 — на АС. Середній вік цих обстежених відповідно склав 45, 32, 42 і 38 років, тривалість захворювання — 10, 4, 12 і 11 років, а співвідношення чоловіків та жінок — 1 : 5, 1 : 1, 1 : 2 і 10 : 1. Результати. СГБ розвивається відповідно у 3, 4, 5 і 9 % від загального числа хворих із РА, ПА, РеА й АС, або в 24, 17, 26 і 27 % від числа таких пацієнтів із ПНП, що тісно пов’язано з наявністю при всіх захворюваннях тендовагінітів та з тяжкістю перебігу суглобового синдрому, при РА залежить від дигітального артеріїту, гіпофункції щитоподібної залози і синдрому Шегрена, при РеА — від порушень збудливості міокарда й електричної провідності серця, при ПА — ексудативної форми шкірного псоріазу, при АС — остеопорозу, а в патогенезі СГБ беруть участь імунні порушення, процеси ендотеліальної дисфункції судин та зміни фізико-хімічних адсорбційно-реологічних в’язкоеластичних й релаксаційних властивостей крові. Висновки. СГБ взаємопов’язаний із клініко-лабораторними ознаками запальних захворювань суглобів, а в майбутньому буде корисним активне виявлення такої патології нервової системи задля подальших своєчасних реабілітаційних заходів, причому серопозитивність артритів за антитілами до циклічного цитрулінового пептиду є чинником ризику такої ПНП.

Serum Inflammatory Markers in Patients with Guillain Barre Syndrome.

Guillain Barre syndrome (GBS) is an immune-mediated peripheral neuropathy characterized by the demyelination and axonal damage of the peripheral neurons. The pathogenesis of GBS involves the breakdown of the blood-brain barrier after which pro inflammatory cytokines attack the neurons in the peripheral nervous system. This study aims to evaluate five markers, namely matrix metalloproteinase (MMP)-2 and MMP-9, vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factor (bFGF), and SFLT-1, which could have a role in the inflammatory response in patients with GBS and healthy controls. In this prospective study, patients diagnosed with GBS at the department of neurology, Kasturba Medical College, Manipal, Karnataka were enrolled. The markers selected for this study were analyzed using the ELISA method and expressed as given in the kit provided by the company. Ethical clearance was obtained from the Institutional Ethical Committee. Results were evaluated using SPSS version 17.0 and expressed as mean ± SD. Error bars for each were drawn. The levels of all five parameters showed a significant increase in patients as compared to controls. Disruption of the basement membrane of endoneurium by MMP-2 and MMP-9, recruitment and migration of macrophages and other cytokines by VEGF-A, bFGF, and soluble fms-like tyrosine kinase-1 (SFLT-1) are plausible, which leads to inflammation process and thus neuronal damage leading to the development of GBS.

GUILLAIN BARRÉ SYNDROME POST SARS-COV-2 INFECTION: A CASE REPORT

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Guillain Barre Syndrome (GBS) is a syndrome usually consisting of paralyzing illness following an infectious process. SARS-COV-2 virus has well documented complications including pneumonia, ARDS, nephropathy, and thrombosis. Neurologic sequelae of GBS, as described in our case are much less common (1). CASE PRESENTATION: An 85-year-old African American male with recent COVID-19 infection, who presented to the emergency department with bilateral lower extremity weakness and bilateral upper extremity tingling for 24 hours. Vital signs were stable on admission. Physical exam revealed quadriparesis and sensory loss, areflexia of L4 and S1 and no saddle anesthesia. MRI brain and cervical spine revealed no signs of myelitis. Due to concern for COVID-19 post viral syndrome in the setting of new, rapidly progressing neurological symptoms, IVIG therapy was initiated. An EMG study was performed and was consistent with length dependent sensory and motor polyneuropathy, with mixed demyelinating and axonal features. Furthermore, there was minimal to absent recruitment of most muscles, consistent with high severity of disease. Patient's condition continued to worsen. He was intubated and placed on mechanical ventilatory support. While on mechanical ventilation, plasma exchange (PLEX) was initiated with subsequent improvement of his symptoms. Eventually, he was transferred to acute inpatient rehab to continue recovery. DISCUSSION: The most common peripheral nervous system manifestations of COVID-19 usually involve anosmia and chemosensory dysfunction (2). Case reports have shown an association between COVID-19 and GBS. It remains unclear whether humoral molecular mimicry, as seen in C. Jejuni, is also the driving mechanism behind the pathogenesis of GBS in SARS-CoV-2 (3). Reports have highlighted that no known SARS-CoV-2 epitopes have been found to be homologically similar to human peripheral nerve tissue and therefore unable to support immune driven, previously widely described molecular mechanisms of GBS (4). However, this lack of clear genetic similarity does not exclude immune mediated response as it's possible that immunogenic proteins could be modified post-translationally or have non-linear antibody epitopes driving such response (5). In addition, although there has been no evidence of SARS-CoV-2 detection in CSF (6), a small sample size of CSF studies from COVID 19 patients likely points towards overall inflammation caused by virus leading to immune cascade and possible infiltration of immune cells locally leading to CNS injury (7). CONCLUSIONS: Clinicians treating COVID-19 viral syndromes should be aware of the association between COVID-19 and GBS, especially when caring for patients with rapidly progressing neurologic disease. Further work needs to be done to broaden the understanding of pathogenesis of GBS in such cases. REFERENCE #1: Montalvan V, Lee J, Bueso T et al. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clinical Neurology and Neurosurgery 194. REFERENCE #2: Lechner M, Chandrasekharan D, Jumani K, Liu et al. Anosmia as a presenting symptom of SARS-CoV-2 infection in healthcare workers - A systematic review of the literature, case series, and recommendations for clinical assessment and management. Rhinology. 2020 Aug 1;58(4):394-399. REFERENCE #3: Loshaj-Shala A, Regazzoni L, Daci A, Orioli M, Brezovska K, Panovska AP, et al. Guillain Barre syndrome (GBS): new insights in the molecular mimicry between C. Jejuni and human peripheral nerve (HPN) proteins. J Neuroimmunology 2015;289: 168–76. DISCLOSURES: No relevant relationships by Mateusz Gorecki, source=Web Response no disclosure on file for Dean Kalam;No relevant relationships by Ahamed Khalyfa, source=Web Response

Guillain-Barré Syndrome and COVID-19: Two Case Reports

[b]BACKGROUND[/b] Since the outbreak of the coronavirus disease 2019 (COVID-19), which subsequently increased to a pandemic, the number of reports about neurological manifestations of the disease has increased. Guillain-Barre syndrome (GBS), which is acute paralytic neuropathy, is one such rare manifestation. [b]CASE REPORT[/b] We report 2 cases of GBS in 58-year-old men with typical manifestations of COVID-19; one of them is presumed COVID-19. The interval between the onset of COVID-19 symptoms and the first symptoms of GBS was 5 and 13 days, respectively. The patients had a more severe GBS than in general cases of GBS associated with COVID-19; they required mechanical ventilation, and both patients developed sepsis and acute kidney injury (AKI), which led to the death of one of them. Serum antiganglioside antibodies were tested in 1 patient and were absent. A nerve conduction study also was performed in 1 patient and confirmed an acute inflammatory demyelinating polyneuropathy. One patient was treated with intravenous immunoglobulin and had a good prognosis, and the other was treated with plasma exchange and died. [b]CONCLUSIONS[/b] Our cases demonstrate the clinical course of GBS in COVID-19, diagnostic findings, and treatment strategies. GBS associated with COVID-19 seems to share most features of other post-infectious GBS. Nevertheless, further research is required to fully understand the characteristics, pathogenesis, and management of GBS in COVID-19.

Cytomegalovirus Infection and Guillain-Barré Syndrome: The First Case-Control Study in Iran.

Objectives Guillain-Barré syndrome (GBS) is an immune-mediated disease of the peripheral nervous system affecting all age groups around the world. Although the pathogenesis and optimal treatment of GBS have not yet been completely identified, one of the most common infectious diseases to trigger the syndrome is cytomegalovirus (CMV) infection. The GBS following CMV infection is rarely reported in childhood, and there have been no data on GBS with antecedent CMV infection in children in Iran. The current study aimed to evaluate the association between CMV infection and GBS in children in Iran. Materials & MethodsThe case-control study design was used for 30 GBS cases and 30 matched controls. All the serum samples were tested for the presence of anti-CMV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies using a commercially available enzyme-linked immunosorbent assay (EUROIMMUN Medizinische, Germany). The CMV viral deoxyribonucleic acid (DNA) in the specimen was detected using polymerase chain reaction (PCR) (Cytomegalovirus PCR Detection Kit, CinnaGen Co., Iran).ResultsAnti-CMV IgG antibodies were detected in 97% of the GBS patients and 93% of the healthy controls. Anti-CMV IgM antibodies were demonstrated in 33% of the healthy controls (n=10) and 33% of the GBS children (n=10). The borderline level of anti-CMV IgM antibodies was observed in 23% of the healthy controls (n=7) and 13% of the GBS children (n=4) (P=0.57). None of the specimens from both controls and GBS cases was positive for CMV DNA using PCR. Conclusion The obtained data demonstrated the presence of anti-CMV antibodies in the majority of both GBS patients and controls. Moreover, no relation was observed between CMV infection and GBS. However, it is highly recommended to perform further studies with a large sample size.

Altered serum levels of IL-36 cytokines (IL-36α, IL-36β, IL-36γ, and IL-36Ra) and their potential roles in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute autoimmune neurological disorder mainly involving the peripheral nerves. Currently, various cytokines have been shown to be involved in the pathogenesis of GBS. Because of their similar biological structures, interleukin (IL)-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist (Ra) were all renamed and collectively called IL-36 cytokines. The roles of IL-36 cytokines in GBS currently remain unclear.Forty-two patients with GBS and 32 healthy volunteers were included in our study. Serum IL-36α, β, γ, and interleukin-36 receptor antagonist (IL-36Ra) levels of patients with GBS in the acute and remission phases and healthy volunteers were measured by enzyme-linked immunosorbent assay (ELISA). In addition, we examined the serum levels of other inflammatory factors that have been shown to be involved in GBS pathogenesis, represented by IL-17 and tumor necrosis factor-α (TNF-α). Furthermore, the correlations between the serum levels of IL-36 cytokines and different clinical data or the serum levels of other inflammatory factors in GBS patients were analyzed.Significantly higher serum IL-36α and IL-36γ levels were measured in the acute phase than in the remission phase and in healthy control (HC) subjects (P < .05), while lower serum IL-36Ra levels were measured in the acute phase than in the remission phase and in HC subjects (P < .05). Serum IL-36α and IL-36γ levels were positively correlated with GBS disability scale scores (GDSs), while serum IL-36Ra levels were negatively correlated with GDSs. Correlation analyses among inflammatory factors showed that serum IL-36α and IL-36γ levels in GBS patients were positively correlated with serum IL-17 and TNF-α levels, while serum IL-36Ra levels were negatively correlated with the levels of these 2 inflammatory factors. Similar results were observed in cerebrospinal fluid (CSF), IL-36α and IL-36γ levels in CSF were positively correlated with GDSs, while IL-36Ra levels in CSF were negatively correlated with GDSs. Additionally, the serum and CSF levels of IL-36α and IL-36γ in the axonal subtype of GBS patients were higher than those in the demyelination subtype.Based on our findings, IL-36 cytokines may be involved in the pathogenesis of GBS and some of these cytokines may help predict the disease severity and other clinical characteristics of GBS.

Antigenic Variability a Potential Factor in Assessing Relationship Between Guillain Barré Syndrome and Influenza Vaccine - Up to Date Literature Review.

Guillain-Barré syndrome (GBS) is a possible serious adverse event of the influenza vaccine but it is yet to be proven. The objective of our traditional literature review is to assess the potential relationship between GBS and influenza vaccine. A traditional literature review has been carried out by selecting 26 articles from PubMed published between 2011 and 2020. Twenty-six articles met the selection criteria (eight observational studies, four systematic literature review, three meta-analyses, two case-control, two retrospective cohort, and seven case series). Selected studies were focused on monitoring the safety of influenza vaccines, the relative safety of pandemic and seasonal influenza vaccines, influenza vaccine a potential etiology of GBS, and pathogenesis of post-vaccination GBS. Few studies have shown a higher incidence of GBS with a pandemic influenza vaccine compared to the seasonal influenza vaccine, while several studies have concluded a small increase in the possibility of GBS following any type of influenza vaccine. There were some studies that estimated no association possibly due to the presence of confounding factors such as influenza-like illness, low power of the study, and reporting bias in post-vaccination surveillance programs. GSB should be taken into consideration as one of the less common but serious side effects of the influenza vaccine but it should not adversely affect the acceptance of the influenza vaccination program. Continuous monitoring of influenza vaccine safety should be performed regularly.

Fulminant Guillain-Barré Syndrome and Spontaneous Intraventricular Hemorrhage: A Case Report and Literature Review.

Guillain–Barré syndrome (GBS) is an acute, immune-mediated inflammatory peripheral polyneuropathy that is characterized by flaccid paralysis. A few cases have reported that GBS can be caused by head trauma or neurosurgery, but it has never been associated with intraventricular hemorrhage. Here, we report an uncommon case of fulminant GBS that occurred after spontaneous intraventricular hemorrhage. A 73-year-old woman was admitted to the hospital after sudden unconsciousness and vomiting. A head computed tomography (CT) scan following the incident showed a newly developed intraventricular hemorrhage, which led to an immediate ventriculostomy. After 5 days, the endotracheal tube was removed. Two days later, the external ventricular drainage tube was also removed. At this time, the patient was alert and the neurological examination was normal. However, the patient suddenly presented with acute respiratory failure and bilateral limb weakness 3 days later. An analysis of the patient’s cerebrospinal fluid (CSF) revealed that albuminocytologic dissociation was present. The patient was treated with intravenous immunoglobulin (0.4 g/kg/day) for 5 days. Despite timely medical intervention in the hospital, the patient passed away 2 months later. After a cerebral hemorrhagic injury, limb and respiratory muscle weakness can occur on occasion in the ICU. In this context, the potential involvement of GBS should not be ignored. Importantly, the pathogenic mechanism of GBS has been discussed for over a century, and it still remains a mystery. We speculate that the TLR4/NF-κB signaling pathway may be involved in the pathogenesis of GBS following intraventricular hemorrhage. The prognosis of most patients with GBS is usually good, but cerebral hemorrhage and mechanical ventilation may serve as risk factors that exacerbate the condition. This case is reported to remind clinicians to consider the possibility of GBS when patients present limb and respiratory muscle weakness after intraventricular hemorrhage, and to provide a starting point to discuss potential mechanisms of GBS after intraventricular hemorrhage.

Fc-gamma IIIa-V158F receptor polymorphism contributes to the severity of Guillain-Barré syndrome.

ObjectiveGuillain‐Barré syndrome (GBS) is a rare, life‐threatening disorder of the peripheral nervous system. Immunoglobulin G Fc‐gamma receptors (FcγRs) mediate and regulate diverse effector functions and are involved in the pathogenesis of GBS. We investigated whether the FcγR polymorphisms FcγRIIa H/R131 (rs1801274), FcγRIIIa V/F158 (rs396991), and FcγRIIIb NA1/NA2, and their haplotype patterns affect the affinity of IgG‐FcγR interactivity and influence GBS susceptibility and severity.MethodsWe determined FcγR polymorphisms in 303 patients with GBS and 302 ethnically matched healthy individuals from Bangladesh by allele‐specific polymerase chain reaction. Pairwise linkage disequilibrium and haplotype patterns were analyzed based on D ´statistics and the genotype package of R statistics, respectively. Logistic regression analysis and Fisher’s exact test with corrected P (Pc) values were employed for statistical comparisons.ResultsFcγRIIIa‐V158F was associated with the severe form of GBS compared to the mild form (P = 0.005, OR = 2.24, 95% CI = 1.28–3.91; Pc = 0.015); however, FcγR genotypes and haplotype patterns did not show any association with GBS susceptibility compared to healthy controls. FcγRIIIa‐V/V158 and FcγRIIIb‐NA2/2 were associated with recent Campylobacter jejuni infection (P ≤ 0.001, OR = 0.36, 95% CI = 0.23–0.56; Pc ≤ 0.003 and P = 0.004, OR = 1.70, 95% CI = 1.18–2.44; Pc ≤ 0.012, respectively). Haplotype 1 (FcγRIIa‐H131R‐ FcγRIIIa‐V158F‐ FcγRIIIb‐NA1/2) and the FcγRIIIb‐NA2/2 genotype were more prevalent among anti‐GM1 antibody‐positive patients (P = 0.031, OR = 9.61, 95% CI = 1.24–74.77, Pc = 0.279; P = 0.027, OR = 1.62, 95% CI = 1.06–2.5, Pc = 0.081, respectively).InterpretationFcγR polymorphisms and haplotypes are not associated with susceptibility to GBS, though the FcγRIIIa‐V158F genotype is associated with the severity of GBS.