Anti-ganglioside Antibodies Research Articles

P345 Another brick in the wall: Is hexane neuropathy a ‘nodo-paranodopathy’?

Objectives To discuss electrophysiological follow-up of patients with n-hexane neuropathy and to remark overlaps with new concept nodo-paranodopathy. Methods 3 males, aged between 18–39 years, working in shoe manufactory were evaluated. Occupational history, toxic substance exposures, neurologic examinations were noted and NCV-EMG were performed upon hospital admission and during clinical follow-up (1., 3., 4., 6. months; 1., 3., 9. months; 3., 4., 5. months, respectively). Results Motor nerve conduction studies, performed in 1–4 months of clinical paresia initiation, revealed focal conduction blocks. Electrophysiological follow-up showed decreased distal CMAP amplitudes and denervation potentials supporting axonal degeneration in some; whereas increment in some other distal CMAP amplitudes, supporting early reversed conduction failures. This different patterns of conduction block resolution were documented both in different nerves of different patients and also in different nerves of the same patient. SNAPs were either decreased or preserved. Urine 2,5-hexandion concentrations were between 1.45–4.52 mg. Discussion n-Hexane gives cause to one of the most common toxic polyneuropathies seen in poorly ventilated factories. It is a sensory-motor polyneuropathy ending up with axonal degeneration. Nerve biopsy reveals paranodal axonal swelling and secondary myelin retraction in early stages. Myelin retraction imitates demyelination causing focal conduction block and failure before axonal degeneration emerges. This brings to mind the new category of nodo-paranodopathy described firstly for anti-ganglioside antibody mediated neuropathies, which can be proved by electrophysiological reevaluations. Significance n-Hexane neuropathy may have a pathogenic mechanism of dysfunction/disruption at the node of Ranvier as another example of nodo-paranodopathy.

O123 Optimizing the electrodiagnostic accuracy in Guillain–Barré syndrome subtypes: Sparse linear discriminant analysis versus criteria sets

Objective To optimize the electrodiagnostic accuracy for Guillain-Barre (GBS) subtypes at the first test and define the criteria for reversible conduction failure (RCF). Methods The reference electrodiagnosis was obtained in 53 demyelinating and 45 axonal GBS patients on the basis of two serial studies and results of anti-ganglioside antibodies assay. We retrospectively employed sparse linear discriminant analysis (SLDA), a supervised statistical method of classification, two existing electrodiagnostic criteria sets (Hadden et al., 1988; Rajabally et al., 2015) and one we propose that additionally evaluates duration of motor responses, sural sparing pattern and RCF in motor and sensory nerves at the second study. Results At first study the misclassification error rates, compared to reference diagnoses, were: 15.3% for sparse SLDA, 30 % for our criteria, 45% for Rajabally’s and 48% for Hadden’s criteria. SLDA identified seven most powerful electrophysiological variables differentiating demyelinating and axonal subtypes and assigned to each patient the diagnostic probabilityof belonging to either subtype. At second test 46.6% of axonal GBS patients showed RCF in two motor and 8.8% in two sensory nerves. Discussion and conclusions Basing on a single test, SLDA showed the highest diagnostic accuracy. Anyway RCF is present in a considerable percentage of axonal GBS patients and can be assessed only with serial tests. Significance Algorithms for SLDA are already available in several statistical packages and even the electromyographic machines could be easily equipped with the appropriated algorithms providing the physician with a decision support system for the diagnosis of neuropathies.

Neuroinfectious Diseases: Guillain Barre Syndrome Clinical Features Suggestive of Early Diagnosis

Guillain Barré syndrome is one of the best examples of a post infectious immune disease and offers insights into the mechanism of tissue damage in other more common autoimmune diseases. Controlled epidemiological studies have linked it to infection with Campylobacter jejuni in addition to other viruses including cytomegalovirus and Epstein Barr virus. The syndrome includes several pathological subtypes, of which the most common is a multifocal demyelinating disorder of the peripheral nerves in close association with macrophages. Evidence from histological examination of peripheral nerve biopsy and postmortem samples suggests that both cell mediated and humoral mechanisms are involved in the pathogenesis. Immunological studies suggest that at least one third of patients have antibodies against nerve gangliosides, which in some cases also react with constituents of the liposaccharide of C jejuni. In the Miller Fisher variant of the disease, these antiganglioside antibodies have been shown to produce neuromuscular block, and may in part explain the clinical signs of that disorder. Treatment with both intravenous immunoglobulin and plasma exchange reduces the time taken for recovery to occur, although mortality remains around 8%, with about 20% of patients remaining disabled.

Transplanted human fecal microbiota enhanced Guillain Barr\xe9 syndrome autoantibody responses after Campylobacter jejuni infection in C57BL/6 mice

BackgroundCampylobacter jejuni is the leading antecedent infection to the autoimmune neuropathy Guillain-Barré syndrome (GBS), which is accompanied by an autoimmune anti-ganglioside antibody attack on peripheral nerves. Previously, we showed that contrasting immune responses mediate C. jejuni induced colitis and autoimmunity in interleukin-10 (IL-10)-deficient mice, dependent upon the infecting strain. Strains from colitis patients elicited T helper 1 (TH1)-dependent inflammatory responses while strains from GBS patients elicited TH2-dependent autoantibody production. Both syndromes were exacerbated by antibiotic depletion of the microbiota, but other factors controlling susceptibility to GBS are unknown.MethodsUsing 16S rRNA gene high-throughput sequencing, we examined whether structure of the gut microbial community alters host (1) gastrointestinal inflammation or (2) anti-ganglioside antibody responses after infection with C. jejuni strains from colitis or GBS patients. We compared these responses in C57BL/6 mice with either (1) stable human gut microbiota (Humicrobiota) transplants or (2) conventional mouse microbiota (Convmicrobiota).ResultsInoculating germ-free C57BL/6 wild-type (WT) mice with a mixed human fecal slurry provided a murine model that stably passed its microbiota over >20 generations. Mice were housed in specific pathogen-free (SPF) facilities, while extra precautions of having caretakers wear sterile garb along with limited access ensured that no mouse pathogens were acquired. Humicrobiota conferred many changes upon the WT model in contrast to previous results, which showed only colonization with no disease after C. jejuni challenge. When compared to Convmicrobiota mice for susceptibility to C. jejuni enteric or GBS patient strains, infected Humicrobiota mice had (1) 10-100 fold increases in C. jejuni colonization of both strains, (2) pathologic change in draining lymph nodes but only mild changes in colon or cecal lamina propria, (3) significantly lower Th1/Th17-dependent anti-C. jejuni responses, (4) significantly higher IL-4 responses at 5 but not 7 weeks post infection (PI), (5) significantly higher Th2-dependent anti-C. jejuni responses, and (6) significantly elevated anti-ganglioside autoantibodies after C. jejuni infection. These responses in Humicrobiota mice were correlated with a dominant Bacteroidetes and Firmicutes microbiota.ConclusionsThese data demonstrate that Humicrobiota altered host-pathogen interactions in infected mice, increasing colonization and Th-2 and autoimmune responses in a C. jejuni strain-dependent manner. Thus, microbiota composition is another factor controlling susceptibility to GBS.

Campylobacter colonization is not associated with proventricular dilatation disease in psittacines.

Psittacine proventricular dilatation disease (PDD) is a neurological disease caused by parrot bornaviruses. A competing theory suggests that intestinal colonization by Campylobacter species may also be a potential cause of PDD or that their presence may be required for disease development. This theory proposes that PDD results from the activities of antiganglioside antibodies on enteric neurons in a manner similar to the pathogenesis of Guillain–Barré syndrome in humans. We therefore cultured feces from domestic chickens as well as from multiple parrot species to determine whether Campylobacter spp. could be detected in the latter. We failed to detect Campylobacter in a flock of cockatiels known to be highly susceptible to experimental parrot bornavirus-induced PDD. Even in naturally infected psittacines suffering from clinical PDD, no Campylobacter species were detected. Conversely, Campylobacter was readily cultured from domestic poultry samples and confirmed by using matrix-associated laser desorption ionization mass spectroscopy/real-time polymerase chain reaction. We conclude that not only are Campylobacter infections of psittacines uncommon, but also that infection by Campylobacter species is not related to the etiology of PDD.

Multifocal Motor Neuropathy Associated With Infliximab

Multifocal motor neuropathy with conduction block (MMN-CB) is purely a motor neuropathy with progressive weakness that is characteristically caused by conduction blocks. Association with antiganglioside antibodies and a good response to immunomodulating therapies suggest an autoimmune etiology. In rare cases, MMN-CB has been reported as an adverse effect of infliximab, a tumor necrosis factor-α blocker. We present a case of MMN-CB due to infliximab in a 45-year-old man with psoriatic arthritis who was exposed to the drug for 2 years because of a delayed diagnosis. We emphasize the possibility of this adverse effect and the importance of detailed electrophysiological examinations, which is supported by a review of the literature.

Early discrimination of sensorimotor Guillain-Barré syndrome into demyelinating or axonal subtype by automated nerve excitability testing.

In the early stage of disease, differentiating acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor sensory axonal neuropathy (AMSAN) using only a conventional nerve conduction studies (NCS) may be difficult. We evaluated the differences in the motor axonal excitability properties of 16 cases of sensorimotor Guillain-Barré syndrome by nerve excitability testing (NET). The antiganglioside antibody assay and follow-up NCS resulted in 12 patients diagnosed as AIDP and 4 patients as AMSAN. Clinical and excitability parameters in each group were compared with those in 30 normal controls. Automated NET with threshold tracking techniques was used to calculate the strength-duration time constant (SDTC), threshold electrotonus (TE), current-threshold relationship (CTR), and recovery cycle (RC) of excitability. Except for subtle changes in excitability parameters, AIDP showed no definitive difference relative to normal controls. Comparison between AMSAN and normal controls also revealed no significant differences in the SDTC, TE, and CTR parameters. However, there were clear differences in some of the RC parameters: the relative refractory period was significantly longer in the AMSAN group than in the AIDP group (4.40 ± 1.11 vs. 3.09 ± 1.01 ms, mean ± SEM; p < 0.001), while superexcitability was significantly less prominent in the AMSAN group (-6.80 ± 10.30 vs. -26.48 ± 1.17%, mean ± SEM; p < 0.001). Our study identified that both AIDP and AMSAN were associated with subtle changes in excitability properties. Nonetheless, the prominent increase in refractoriness in AMSAN suggests the presence of a nodal conduction block.

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

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

A case of Anti Ganglioside antibody negative Bickerstaff’s Brainstem Encephalitis-Miller Fisher overlap syndrome (P6.129)

A case of Anti Ganglioside antibody negative Bickerstaff’s Brainstem Encephalitis-Miller Fisher overlap syndrome (P6.129)

Are anti-ganglioside antibodies associated with proventricular dilatation disease in birds?

The identification of Parrot bornaviruses (PaBV) in psittacine birds with proventricular dilatation disease (PDD) has not been sufficient to explain the pathogenesis of this fatal disease, since not all infected birds develop clinical signs. Although the most accepted theory indicates that PaBV directly triggers an inflammatory response in this disease, another hypothesis suggests the disease is triggered by autoantibodies targeting neuronal gangliosides, and PDD might therefore resemble Guillain-Barré Syndrome (GBS) in its pathogenesis. Experimental inoculation of pure gangliosides and brain-derived ganglioside extracts were used in two different immunization studies. The first study was performed on 17 healthy chickens (Gallus gallus domesticus): 11 chickens were inoculated with a brain ganglioside extract in Freund’s complete adjuvant (FCA) and six chickens inoculated with phosphate-buffered saline. A second study was performed five healthy quaker parrots (Myiopsitta monachus) that were divided into three groups: Two quaker parrots received purified gangliosides in FCA, two received a crude brain extract in FCA, and one control quaker parrot received FCA alone. One chicken developed difficult in walking. Histologically, only a mild perivascular and perineural lymphocytic infiltrate in the proventriculus. Two quaker parrots (one from each treatment group) had mild lymphoplasmacytic encephalitis and myelitis. However, none of the quaker parrots developed myenteric ganglioneuritis, suggesting that autoantibodies against gangliosides in birds are not associated with a condition resembling PDD.

Association of anti-gangliosides antibodies and anti-CMV antibodies in Guillain-Barré syndrome.

IntroductionNumerous types of infection were closely related to GBS, mainly including Campylobacter jejuni, Cytomegalovirus, which may lead to the production of anti‐gangliosides antibodies (AGA). Currently, although there are increased studies on the AGA and a few studies of anti‐CMV antibodies in GBS, the association between them remains poorly documented. Therefore, our research aims to analyze the correlation of anti‐CMV antibodies and AGA in GBS.MethodsA total of 29 patients with GBS were enrolled in this study. The CMV antibodies were tested by the electrochemiluminescence immunoassay “ECLIA” (Roche Diagnostics GmbH). The serum gangliosides were determined by The EUROLINE test kit.ResultsOf the 29 patients with GBS, 9 (31%) were AGA‐seropositive, in which 22 were CMV‐IgG positive in CSF at the same time, but all 29 samples were CMV‐IgM negative in both serum and CSF. In the AGA‐positive group, the rate of both serum and CSF positive was 87.5% (7/8), higher than 50% (7/14) of the negative group, although no statistical significance was found. In addition, we found that there was a trend of higher ratio of men, a younger age onset, less frequent preceding infection, a higher level of CSF proteins, and less frequent cranial nerve deficits, although the data did not reach a statistical significance.ConclusionIn spite of no statistical significance association was found between serum AGA and CMV‐IgG in serum and CSF. However, we found that there was a trend of high positive rate of both serum and CSF‐CMV‐IgG in AGA‐positive than the negative group. So we should further expand the sample size to analyze the association between AGA and CMV or other neurotropic virus antibodies in various diseases, to observe whether they could be serological marker of these diseases (especially GBS) or the underlying pathogenesis.

Memory B cells in Guillain-Barré syndrome

IgG autoantibodies against gangliosides show the highest titers at the disease onset of axonal Guillain-Barré syndrome (GBS), in which there are no IgM anti-ganglioside antibodies. We hypothesized that memory B cells take part in the development of producing IgG autoantibodies. In this study, we analyzed the memory B cells in patients with GBS using flow cytometry. There was significantly higher percentage of memory B cells in patients with GBS than the healthy controls. The Spearman correlation analysis demonstrated that increased percentage of memory B cells was positively correlated with the clinical severity of the patients with GBS. Our study provides the evidences that memory B cells may be involved in mechanism of GBS.

Anti-ganglioside antibodies profile in Guillain-Barré syndrome: Correlation with clinical features, electrophysiological pattern, and outcome.

Guillain-Barré syndrome (GBS) and its subtypes are associated with distinct anti-ganglioside antibodies. Hence, we aimed to determine the frequency of anti-ganglioside antibodies and its correlation with clinical features, electrophysiological patterns, and outcome in patients with GBS. The data regarding clinical features, electrophysiological patterns, and outcome at 6 months were collected and analyzed from the case records of patients diagnosed with GBS during 2008-2013 at a tertiary care hospital in south India. A total of 204 patients with GBS were studied, and 73 patients (mean age: 37.6 ± 17.5 years) who underwent anti-ganglioside antibody testing were analyzed. Male-to-female ratio was 2.5:1. IgG anti-ganglioside antibodies were positive in 41/73 patients. The most common IgG anti-ganglioside antibody observed in the acute demyelinating variant was anti-GT1b (n = 13; 17.8%), and, those in the acute axonal variant were anti-GM1, anti-GM2, anti-GD1b, and anti-GT1b antibodies (n = 9;12.3% each). Three patients died and 5 patients were unable to walk independently at the end of 6 months. The frequency of anti-ganglioside antibodies in our cohort with GBS was 56%, with IgG anti-GT1b antibody being the most common. The anti-ganglioside antibodies were significantly positive in acute motor axonal neuropathy (AMAN) subtype of GBS. The presence of anti-ganglioside antibodies was not found to be of significant use in predicting the outcome. Although it was observed that the absence, and not the presence, of anti-ganglioside antibodies was associated with antecedent infection, dysautonomia, and requirement of ventilator support, the overall disease severity was not antibody dependant.

A Patient with Post Infectious Immune Mediated Neuropathy (Miller Fisher Syndrome)

The Miller Fisher variant is an uncommon but well known syndrome being described as a triad of areflexia, ataxia and complex ophthalmoplegia. It is characterized by antibodies against myelin that affects peripheral nerves, extraocular muscles and Schwann cells. Anti-ganglioside antibodies have been recognized in disease pathogenesis and decreasing antibody production is the mainstay of treatment. The course is usually benign with improvement after immunomodulation. This case report describes the approach to a patient suspected of having a demyelinating disorder. It delineates the subsets of immune mediated neuropathies in evaluating the diagnosis and emphasizes the need for early therapeutic intervention in achieving a good clinical outcome.

Guillian-Barre syndrome and variants: Antiganglioside antibodies.

Guillian-Barre syndrome and variants: Antiganglioside antibodies.

Agrupación de casos de síndrome de Guillain-Barré atípico: ¿es necesario redefinir los criterios diagnósticos y los protocolos microbiológicos?

Guillain-Barre syndrome is classically defined as a symmetrical ascending acute polyradiculoneuropathy, although there are atypical variants that make diagnosis difficult. The medical data of six patients in our hospital area are collected during the first quarter of 2013. Lumbar punctures, imaging, neurophysiological studies, ganglioside antibodies and serologies have been proposed in all cases. We focus on the atypical features as late hyporeflexia, increased frequency of asymmetry and distal paresis and initial fever. From a neurophysiological point of view, all patients presented sensorimotor axonal forms. The most consistent datas in early studies is the F wave's alteration. A Miller Fisher variant associated with faciocervicobraquial paresis and cerebral reversible vasoconstriction syndrome has been detected. A bilateral brachial paresis and lumbar polyradiculopathy in the context of influenza A infection is other interesting case. The saltatory variant with cranial nerve involvement and lower limbs paresis has been demonstrated in one patient. Bands in cerebrospinal fluid are positive in three cases and anti-ganglioside antibodies in one patient. The syndrome of inappropriate secretion of antidiuretic hormone may explain some of the hyponatremias registered. The first line of treatment are inmunoglobulins in all patients. Plasmapheresis exchanges has been used as an additional therapy in four cases. These clusters of six axonal cases with atypical clinical features justifies the need for knowledge of these variants in order to achieve an early treatment. Late hyporeflexia and brachialfaciocervico, saltatory and lumbar forms should be considered in the spectrum of Guillain-Barre syndrome. The etiological study should rule out a lots of pathogens as influenza A.

Detection of Naturally Occurring Human Antibodies Against Gangliosides by ELISA.

Gangliosides are sialic acid-containing glycolipids that have been considered attractive targets for cancer immunotherapy, based on the qualitative and quantitative changes they suffer during malignant transformation and due to their importance for tumor biology. Natural antibodies against gangliosides have been detected not only in cancer patients but also in healthy donors. The presence of these antibodies can be used as diagnostic or prognostic factor. However, these responses are difficult to detect because anti-ganglioside antibodies are usually of IgM isotype and low affinity. Enzyme Linked Immunosorbent Assay (ELISA) is an immunoassay based on the specific binding of antibodies to antigens bound to a solid phase. These antigens can be glycolipids like gangliosides. An enzyme linked to the last reactant allows the detection of specific binding through the development of color after the addition of a suitable substrate. ELISA combines the specificity of antibodies with the sensitivity of enzyme reactions. The ELISA method described herein can be used to detect antibody responses against gangliosides not only related to cancer but also to autoimmune diseases and infections, both in healthy donors, and patients, untreated or receiving specific immunotherapy.

Uveitis in Miller Fisher Syndrome—A Case Report and Literature Review

Purpose: To report an unusual case of Miller Fisher Syndrome (MFS) in which the patient presented with concurrent right eye uveitis. Case Report: We report a case of a 51-year-old gentleman who presented with typical clinical features of Miller Fisher syndrome including ophthalmoplegia, ataxia, areflexia, ptosis and diplopia following an upper respiratory tract infection. Concurrently, he also had right eye uveitis with raised intraocular pressure. The patient was treated with intravenous immunoglobulin (IVIG), topical steroids and anti-glaucoma eye drops in which he demonstrated good recovery. For diagnostic confirmation, serum antiganglioside antibodies (anti-GQ1b IgG) were later reported to be positive. Conclusion: We described the possible association between MFS and uveitis due to its interrelated pathogenesis. This possible association can lead to early detection and treatment of uveitis.

Syndrome De Guillain-Barré Chez L’enfant Dans Un Contexte A Ressources Limitées : A Propos De Deux Observations Au CHU Sylvanus Olympio De Lomé - TOGO

Guillain-Barré syndrome is rare in children. With polyvalent immunoglobulins the management and prognosis has been significantly improved with complete recovery rate exceeding 80%. We report the cases of two children who completely recovered after Guillain-Barré syndrome in the absence of immune globulin. He was a 12 year old daughter and an infant of 17 months male who presented a progressive ascending motor deficit, dysphonia with difficulty swallowing, difficulty breathing, areflexia. A albumino-cytological dissociation was found in the study of cerebrospinal fluid in both cases. Electromyography in the girl had confirmed a axono-form myelin. Retroviral serology was negative in both cases. Other serology (Campylobacter jejuni, Cytomegalovirus, Epstein Barr, ZIKA), the dosage of anti-ganglioside antibodies and brain imaging had not been made. The immunoglobulins are not available in our work context, we conducted a symptomatic management. Complete healing was achieved with a 4-month decline.

Anti-ganglioside antibodies in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy in Chinese patients.

In this study we investigated the relationships between anti-ganglioside antibodies and Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Samples from 48 Chinese patients diagnosed with GBS and 18 patients diagnosed with CIDP were retrospectively reviewed. In the GBS patients, 62.5% were classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 27.1% were found to have acute motor axonal neuropathy (AMAN), and 10.4% were unclassified. Serum IgG anti-ganglioside antibodies were detected in 46.2% of the AMAN patients and in 6.7% of the AIDP patients (P < 0.05); 5.6% of the 18 CIDP patients were IgG antibody positive, and 27.8% were IgM antibody positive. Facial palsy and sensory impairment were significantly associated with IgM antibodies. These results suggest that IgG anti-GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55: 470-475, 2017.