An update on pathobiologic roles of anti-glycan antibodies in Guillain-Barré syndrome.

Anti-glycan antibodies directed against gangliosides are now considered the major immune effectors that induce damage to intact nerve fibers in some variants of the monophasic neuropathic disorders that comprise Guillain-Barré syndrome. Recent experimental studies elucidating the complexity of anti-glycan antibody-mediated pathobiologic effects on intact and injured nerves undergoing repair are discussed.

Repeated spinal anesthesia in a tetraparetic patient with Guillain-Barré syndrome

A 78 year old man with tetraparesis, reduced forced vital capacity, and neurogenic bladder dysfunction due to Guillain-Barré syndrome was admitted for elective transurethral prostate resection and percutaneous lithotripsy of a bladder stone. On the sixth postoperative day, he was readmitted for emergency evacuation of a clot in the bladder. Both operations were performed with spinal anesthesia (hyperbaric bupivacaine + fentanyl) without neurologic sequelae.

A case of central nervous system vasculitis related to an episode of Guillain-Barrè syndrome

The authors report their knowledge about an uncommon case of isolated vasculitis, restricted to the left sylvian artery during an auto-immune Guillain-Barrè syndrome (GBS), sustained by cytomegalovirus (CMV). An acute cardiopulmonary failure requiring a ventilator and vasopressor support manifested, notwithstanding plasma exchanging and immune-modulating therapy. An IgM-enriched formula administration coincided with a rapid amelioration of GBS and vasculitis to a complete recovery the next month after her discharge to a rehabilitation centre.

Guillain-Barré Syndrome with Absent Brainstem Reflexes: a Case Report

A 41-year-old man was admitted to an intensive care unit following respiratory arrest. One day prior to admission, he had complaints of nausea and pain involving lower limbs. On the night of admission he developed diplopia, dysphagia, and rapidly progressive quadriparesis. He developed respiratory failure requiring mechanical lung ventilation 24 hours later. On the fifth day of hospital stay the patient became comatose with absent brainstem reflexes and appeared to be brain dead. The cerebrospinal fluid showed albuminocytological dissociation. The electroencephalogram revealed an alpha rhythmical activity. The electrophysiological evaluation revealed an inexcitability of all nerves. Guillain-Barré syndrome was suspected. With supportive treatment the patient had a remarkable recovery and now is able to independently conduct his daily activities.

Síndrome de Guillain-Barré: epidemiologia, prognóstico e fatores de risco

Introduction. Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy and the principal cause of acute neuromuscular paralysis. The most prominent GBS subtypes are: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN) and Fisher syndrome (FS). Differences in geographical distribution of variants have been reported. In Brazil, there are few studies describing the characteristics of GBS, but none on the frequency of GBS variants and their clinical manifestations. Infection-induced aberrant immune response resulting from molecular mimicry and formation of cross-reacting antibodies, contribute to complement activation. Functional biallelic polymorphism in immunoglobulin receptors that influence the affinity of IgG subclasses and the type of immune response have been described, suggesting genetic susceptibility to developing disease. It remains unclear whether individuals carrying different FCGR alleles have differential risk for GBS and⁄or disease severity. The goals of this study were: (1) To characterize GBS and describe the clinical findings in a cohort of patients with GBS from the state of Rio Grande do Norte, Brazil; (2) to determine whether polymorphism in FCGR were associated with development of GBS, and (3) to tease out whether the global gene expression studies could be a tool to identify pathways and transcriptional networks which could be regulated and decrease the time of disease. Methods. Clinical and laboratory data for 149 cases of GBS diagnosed from 1994 to 2013 were analyzed. Genomic DNA and total RNA were extracted from whole blood. Antigangliosides antibodies were determined in the sera. In addition, we also assessed whether FCGR polymorphism are present in GBS (n=141) and blood donors (n=364), and global gene expressions were determined for 12 participants with GBS. Blood samples were collected at the diagnosis and post-recovery. Results. AIDP was the most frequent variant (81.8%) of GBS, followed by AMAN (14.7%) and AMSAN (3.3%). The incidence of GBS was 0.3 ⁄ 100,000 people for the state of Rio Grande do Norte and cases occurred at a younger age. GBS was preceded by infections, with the axonal variant associated with episodes of diarrhea (P = 0.025). Proximal weakness was more frequent in AIDP, and distal weakness predominant in the axonal variant. Compared to 42.4% of cases with AIDP (P<0.0001), 84.6% of cases with the axonal variant had nadir in <10 days. Individuals with the axonal variant took longer to recover deambulation (P<0.0001). The mortality of GBS was 5.3%. A worse outcome was related to an axonal variant (OR17.063; P=0.03) and time required to improve one point in the Hughes functional scale (OR 1.028; P=0.03). The FCGR genotypes and allele frequencies did not differ significantly between the patients with GBS and the controls (FCGR2A p=0.367 and FCGR3A p=0.2430). Global gene expression using RNAseq showed variation in transcript coding for protein isoforms during acute phase of disease. Conclusions. The annual incidence of GBS was 0.3 per 100,00 and there was no seasonal pattern. A predominance of the AIDP variant was seen, and the incidence of the disease decreased with age. The distribution of weakness is a function of the clinical variants, and individuals with the axonal variant had a poorer prognosis. Early diagnosis and variant identification leads to proper intervention decreasing in long-term morbidity. FCGR polymorphisms do not seem to influence susceptibility to GBS in this population. This study found deregulated genes and signs of transcriptional network alterations during the acute and recovery phases in GBS. Identification of pathways altered during disease might be target for immune regulation and with potential to ameliorate symptoms.

Características epidemiológicas del síndrome de Guillain-Barré en población chilena: estudio hospitalario en un período de 7 años

El propósito de este estudio es entregar información que contribuya a la caracterización del síndrome de Guillain-Barré en Chile.

Isolation and genotype analysis of rubella virus from a case of Guillain-Barre syndrome

Rubella virus (RV) infection has sporadically been linked to Guillain-Barre syndrome (GBS), but the association with RV has been based only on clinical and/or serological backgrounds. In the present case it was possible to isolate RV (genotype 1a) from cerebrospinal fluid and peripheral blood mononuclear cells of an 18-year-old woman diagnosed with GBS after clinical manifestations of rubella. This report contributes to confirm RV as one of the triggering pathogens of this peripheral nervous system disease. (C) 2008 Elsevier B.V. All rights reserved.

Nervous system dysfunction in Henoch-Schonlein syndrome: systematic review of the literature

OBJECTIVE: CNS or peripheral nervous system dysfunction sometimes occurs in Henoch-Schönlein patients. METHODS: We review all Henoch-Schönlein cases published after 1969 with CNS dysfunction without severe hypertension and neuroimaging studies (n = 35), cranial or peripheral neuropathy (n = 15), both CNS and peripheral nervous system dysfunction without severe hypertension (n = 2) or nervous system dysfunction with severe hypertension (n = 2). Forty-four of the 54 patients were <20 years of age. RESULTS: In patients with CNS dysfunction without or with severe hypertension the following presentations were observed in decreasing order of frequency: altered level of consciousness, convulsions, focal neurological deficits, visual abnormalities and verbal disability. Imaging studies disclosed the following lesions: vascular lesions almost always involving two or more vessels, intracerebral haemorrhage, posterior subcortical oedema, diffuse brain oedema and thrombosis of the superior sagittal sinus. Following lesions were noted in the subjects with cranial or peripheral neuropathy without severe hypertension: peroneal neuropathy, peripheral facial palsy, Guillain-Barré syndrome, brachial plexopathy, posterior tibial nerve neuropathy, femoral neuropathy, ulnar neuropathy and mononeuritis multiplex. Persisting signs of either CNS (n = 9) or peripheral (n = 1) nervous system dysfunction were sometimes reported. CONCLUSIONS: In Henoch-Schönlein syndrome, signs of nervous system dysfunction are uncommon but clinically relevant. This review helps clinicians managing Henoch-Schönlein syndrome with nervous system dysfunction.

Studies of HLA associations in male and female patients with Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

HLA associations are found to differ with the gender of the patient in some autoimmune diseases. Here we have investigated whether there are gender-related HLA associations in Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), both of which occur more frequently in male patients than in females. In GBS, no particular HLA associations were noted, except for a slight negative association in both males and females for carriage of HLA-DR5. In CIDP, the gene frequency and the frequency of individuals positive for HLA-DR2 were greater in female patients than female controls, although this was statistically significant only for the gene frequency. Furthermore more female CIDP patients were homozygous for DR2, than male CIDP patients, or male or female controls and patients with GBS. This suggests that sex-related factors may interact with the risk associated with carriage of HLA-DR2 for development of CIDP. (c) 2006 Published by Elsevier B.V.

Plasmapheresis vs. immunoglobulin in autoimmune neurologic diseases: a meta-analysis

Objectives: to evaluate the efficacy and safety of human immunoglobulin versus plasmapheresis in the management of autoimmune neurologic diseases. Likewise, length of hospital stay and duration of ventilator support were compared. Methods: Randomized controlled trials and analytical observational studies of more than 10 cases, were reviewed. Cochrane Neuromuscular Disease Group trials, MEDLINE, EMBASE, HINARI Ovid, the Database of abstracts of reviews of effectiveness and the Economic evaluation Database were searched as data source. Reference lists were examined for further relevant articles. A random-effect model was used to derive a pooled risk ratio. Results: 725 articles were found and 27 met the criteria for a population studied of 4717 cases: 14 articles were about Guillain Barré syndrome, 10 of Myasthenia Gravis, one of Sydenham Chorea, one of Chronic inflammatory demyelinating polyneuropathy, and one of PANDAS. No evidence was found in favor of any of the two treatments as regards effectiveness (OR 0.94, IC 0.63 – 1.41, p= 0.77) or ventilator support time; IGIV had a significant better safety profile than plasmapheresis (OR 0.70, IC 0.51 – 0.96, p= 0.03) and patients needed less time of hospital stay (p=0.03). Conclusions: There is no evidence for superiority in the effectiveness of immunoglobulin or plasmapheresis in the management of autoimmune neurologic diseases. Nevertheless, patients treated with immunoglobulin have statistically significant less adverse effects, a shorter hospital stay and a tendency of less ventilator support time. These premises could lead to fewer costs for health services but an economic study should be done.

Caratterizzazione clinica, eziopatogenetica e ricerca di marker diagnostici nella poliradicoloneurite acuta idiopatica del cane

La poliradicoloneurite acuta idiopatica (ACIP) è una patologia infiammatoria che interessa le radici di più nervi spinali, descritta soprattutto nel cane, più raramente nel gatto, caratterizzata da insorgenza acuta di paresi/paralisi flaccida. L’ACIP mostra notevoli similitudini con la sindrome di Guillan-Barrè dell’uomo (GBS), in cui la patogenesi è su base autoimmunitaria ed è stata correlata con la presenza di alcuni fattori scatenanti (trigger). Lo scopo di questo lavoro è stato quello di caratterizzare l’ACIP in 26 cani, descrivendone la sintomatologia, l’evoluzione clinica, i risultati degli esami diagnostici. La diagnosi si è basata sui riscontri dell’anamnesi, della visita neurologica e del decorso confermata, quando possibile, dai rilievi elettrodiagnostici. Su tutti i cani è stata valutata l’esposizione a specifici agenti infettivi (Toxoplasma gondii, Neospora canunim, Ehrlichia canis, Leishmania infantum), o altri fattori (come vaccinazioni) che potrebbero aver agito da “trigger” per l’instaurarsi della patologia; sull’intera popolazione e su 19 cani non neurologici (gruppo di controllo), si è proceduto alla ricerca degli anticorpi anti-gangliosidi. La sintomatologia di più frequente riscontro (25/26) ha coinvolto la funzione motoria (paresi/plegia) con prevalente interessamento dei 4 arti (24/25) . Sei cani hanno ricevuto una terapia farmacologica, che non ne ha influenzato il decorso, favorevole in 24/26 casi. In 9 pazienti è stata rilevata una precedente esposizione a potenziali trigger; in 10 casi si è riscontrato un titolo anticorpale positivo ad almeno un agente infettivo testato. In 17/26 cani si è ottenuto un titolo anticorpale anti-GM2 e anti-GA1; nella popolazione di controllo solo un caso è risultato positivo. Questi risultati hanno contribuito a consolidare le conoscenze di questa patologia, validando l’utilità della ricerca anticorpale anti-gangliosidica per la diagnosi di ACIP e facendo intravedere la possibilità che l’ACIP possa essere assimilate alla GBS anche dal punto di vista patogenetico, per la quale potrebbe essere considerata come modello animale spontaneo.

Monospecific high-affinity and complement activating anti-GM1 antibodies are determinants in experimental axonal neuropathy

It has been difficult to replicate consistently the experimental model of axonal Guillain-Barré syndrome (GBS). We immunized rabbits with two lipo-oligosaccharides (LOS1 and LOS2) derived from the same C. jejuni strain and purified in a slightly different way. LOS1 did not contain proteins whereas several proteins were present in LOS2. In spite of a robust anti-GM1 antibody response in all animals the neuropathy developed only in rabbits immunized with LOS1. To explain this discrepancy we investigated fine specificity, affinity and ability to activate the complement of anti-GM1 antibodies. Only rabbits immunized with LOS1 showed monospecific high-affinity antibodies which activated more effectively the complement. Although it is not well understood how monospecific high-affinity antibodies are induced these are crucial for the induction of experimental axonal neuropathy. Only a strict adherence to the protocols demonstrated to be successful may guarantee the reproducibility and increase the confidence in the animal model as a reliable tool for the study of the human axonal GBS.