gq1b-ganglioside and Syndrome

Miller-Fisher syndrome and Bickerstaff brainstem encephalitis, among others, constitute the anti-GQ1b syndrome, with a common immune pathophysiologic pathway characterized by the presence of anti-GQ1b antibodies, which react against the different nervous system GQ1b sites according to their different accessibility. The Miller-Fisher syndrome has a prevalence of 0.09 cases per 100 000 people-year but there are not epidemiological studies about Bickerstaff brainstem encephalitis, that it seems to be less frequent. In spite of having a good natural outcome, the immunoglobulin administration has been established as efficacious at improving it. A twelveyear- old boy suffering from Miller-Fisher-Bickerstaff syndrome after an acute Campylobacter jejuni diarrhea with positive titers of anti-GQ1b and anti-QGT1a antibodies is presented. We communicate a very uncommon pediatric disease with the aim of warning about the importance of its early suspicion and the need of specific laboratory determinations.. El síndrome anti-GQ1b reúne el síndrome de Miller-Fisher y la encefalitis del tronco cerebral de Bickerstaff, entre otras entidades. Tienen etiopatogenia común, constituida por la presencia de anticuerpos anti-GQ1b que reaccionan contra los sitios GQ1b del sistema nervioso según sea su accesibilidad. La prevalencia anual del síndrome de Miller-Fisher es de 0,09 casos por 100 000 habitantes por año y no existen estudios epidemiológicos sobre la encefalitis del tronco cerebral de Bickerstaff, que sería menos frecuente. De evolución natural hacia la mejoría, se beneficia del tratamiento con gammaglobulina endovenosa. Se presenta a un paciente de 12 años con síndrome de Miller- Fisher–Bickerstaff tras un episodio de diarrea aguda por Campylobacter jejuni en el que los anticuerpos anti-GQ1b resultaron positivos. Es nuestro objetivo comunicar sobre un síndrome de presentación poco habitual en pediatría a fin de advertir acerca de la necesidad de su sospecha precoz y solicitud de estudios de laboratorio específicos.

Topics: Autoantibodies; Autoantigens; Biomarkers; Child; Encephalitis; Gangliosides; Humans; Male; Miller Fisher Syndrome; Syndrome

Anti-GQ1b antibody syndrome encompasses Miller Fisher syndrome and its related disorders. We retrospectively identified 11 pediatric patients (5.4-18 years old) with anti-GQ1b antibody syndrome. Diagnoses of patients included acute ophthalmoparesis (n = 6), classical Miller Fisher syndrome (n = 2), Miller Fisher syndrome/Guillain-Barré syndrome (n = 1), acute ataxic neuropathy (n = 1), and pharyngeal-cervical-brachial weakness (n = 1). Nine patients (81.8%) fully recovered. Maturational change in GQ1b antigen expression and the accessibility of anti-GQ1b antibodies might be the cause of the difference of clinical manifestations in children with anti-GQ1b antibody syndrome.

Topics: Adolescent; Autoantibodies; Child; Child, Preschool; Female; Gangliosides; Humans; Male; Miller Fisher Syndrome; Ophthalmoplegia; Republic of Korea; Retrospective Studies; Syndrome

Anti-GQ1b antibodies can be detected in the serum of patients with Miller Fisher syndrome (MFS) and its incomplete forms such as acute ophthalmoparesis (AO), acute ptosis, acute mydriasis, acute oropharyngeal palsy and acute ataxic neuropathy (AAN), as well as in pharyngeal-cervical-brachial weakness, Bickerstaff brainstem encephalitis (BBE) and in overlap syndromes with Guillain-Barré syndrome (MFS-GBS, BBE-GBS). We searched the laboratory medicine database at University Hospitals Leuven between 2002 and 2017 for serum samples with anti-GQ1b IgG antibodies. We identified eight patients with anti-GQ1b antibodies: 4 MFS, 2 AO, 1 MFS-GBS and 1 AAN. Mean age was 57 years and five patients were males. Preceding illness was present in all patients. At nadir, we observed most frequently gait disturbance, external ophthalmoplegia and absent/decreased reflexes. Albumino-cytological dissociation was present in four patients. Mean time between onset and nadir was 4 days, between onset and recovery 2.5 months. Five patients recovered completely and three had minor residual symptoms. Interestingly, one patient with AO experienced a second identical episode, approximately 1 year after the first one. Our data confirm the broad clinical spectrum associated with the presence of anti-GQ1b IgG antibodies. Incomplete MFS subtypes such as AO are a challenge for diagnosis, because of the limited (though invalidating) clinical presentation and the lack of confirming ancillary tests. Subacute onset of ophthalmoplegia and/or ataxia should urge the clinician to include the anti-GQ1b antibody syndrome in the differential diagnosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Autoantigens; Autoimmune Diseases; Female; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Miller Fisher Syndrome; Ophthalmoplegia; Paraplegia; Syndrome; Young Adult

Topics: Adult; Autoantibodies; Gangliosides; Humans; Male; Ophthalmoplegia; Recurrence; Syndrome

Anti-GQ1b IgG antibody syndrome comprises a wide range of diseases presenting with ophthalmoplegia and ataxia. Anti-GQ1b antibodies have been strongly associated in the literature with Miller Fisher Syndrome, with acute ophthalmoplegia associated with Guillain-Barré syndrome, and with isolated ophthalmoplegia. Acute ophthalmoplegia presents as various combinations of external and internal ophthalmoplegia. Reported here is a novel case of isolated ptosis as a manifestation of ophthalmoplegia. The present finding of bilateral ptosis and areflexia with anti-GQ1b IgG antibody positivity helps confirm the existence of the syndrome. Further research is needed on diagnosis and treatment.

Topics: Acute Disease; Ataxia; Autoantibodies; Autoimmune Diseases of the Nervous System; Blepharoptosis; Child, Preschool; Gangliosides; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Immunologic Factors; Male; Ophthalmoplegia; Reflex; Syndrome; Treatment Outcome

Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barré syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO). The aim of this study was to determine the clinical features of AO associated with anti-GQ1b antibody.. We retrospectively collected 34 patients with anti-GQ1b antibody syndrome. Of these patients, 31 patients had ophthalmoplegia. The patients with ophthalmoplegia were classified into MFS (n = 13), AO (n = 11), GBS with ophthalmoplegia (n = 6), and BBE (n = 1). We analyzed clinical features and patterns of external and internal ophthalmoplegia of AO, and neuro-ophthalmologic findings were compared with those of other anti-GQ1b syndromes with ophthalmoplegia.. AO was observed in 11 (32.4%) of the 34 patients with anti-GQ1b antibody. External ophthalmoparesis was present in all the patients and included mixed horizontal-vertical (n = 7), pure horizontal (n = 3), and pure vertical gaze palsy (n = 1). Binocular involvement was common, but unilateral ophthalmoparesis was also observed in 27.3%. Other findings included ptosis (n = 5, 45.5%) and internal ophthalmoplegia (n = 6, 54.5%). Other anti-GQ1b antibody syndromes had prominent neurologic signs including ataxia, weakness, and facial palsy in addition to ophthalmoplegia. The patterns of neuro-ophthalmologic findings did not differ between AO and other anti-GQ1b antibody syndromes with ophthalmoplegia.. Acute ophthalmoplegia (AO) commonly occurs in anti-GQ1b antibody syndrome and manifests as various combinations of external and internal ophthalmoplegia. Internal ophthalmoplegia is fairly common and unilateral involvement may occur in AO.

Topics: Acute Disease; Adolescent; Aged; Autoantibodies; Female; Gangliosides; Humans; Male; Middle Aged; Ophthalmoplegia; Retrospective Studies; Syndrome

Bickerstaff brainstem encephalitis is characterized by the occurrence of ataxia, ophthalmoplegia, motor weakness with areflexia and central nervous system symptoms, with drowsiness, pyramidal syndrome and sensorial symptoms. Diagnosis is based on MR findings and GQ1b antibodies. Treatment is not well known.. We report a patient aged 39 years native of Laos who presented weakness, loss of reflexes, and drowsiness. Brain MR showed hyperintense signals in the brain stem. GQ1b antibodies were positive. The course was characterized by decrease of the weakness, normalization of MR and negativity of GQ1b antibodies.. This observation underlines common features of Bickerstaff brainstem encephalitis, Miller Fisher syndrome and Guillain Barre syndrome. A favorable course and GQ1b antibodies are shared by these syndromes.

Topics: Adrenal Cortex Hormones; Autoantibodies; Autoantigens; Blindness; Brain Stem; Coma; Combined Modality Therapy; Demyelinating Autoimmune Diseases, CNS; Electroencephalography; Encephalitis; Female; Gangliosides; Humans; Magnetic Resonance Imaging; Middle Aged; Optic Atrophy; Plasmapheresis; Quadriplegia; Reflex, Abnormal; Syndrome

The Miller Fisher syndrome, Guillain-Barre syndrome and Bickerstaff's brainstem encephalitis are related conditions in which anti-GQ1b antibody positivity occur in varied frequencies. This report demonstrates the presence of corticobulbar and corticospinal dysfunction in BBE, by means of a novel transcranial magnetic stimulation technique. It further supports the presence of protean manifestations in anti-GQ1b IgG antibody-positive spectrum of disorders.

Topics: Adult; Autoantibodies; Brain Stem; Dysarthria; Encephalitis; Evoked Potentials, Motor; Gangliosides; Guillain-Barre Syndrome; Humans; Hypoglossal Nerve; Hypoglossal Nerve Diseases; Male; Motor Neurons; Neural Conduction; Neurologic Examination; Pyramidal Tracts; Reaction Time; Reflex, Abnormal; Remission, Spontaneous; Syndrome; Tongue; Transcranial Magnetic Stimulation

Topics: Adult; Antibody Formation; Disease Progression; Female; Gangliosides; Humans; Miller Fisher Syndrome; Phenotype; Recurrence; Syndrome

Sera from patients with Fisher's syndrome in the acute phase contain immunoglobulin (Ig)G anti-GQ1b ganglioside antibody. Removal of the autoantibody should lead to earlier recovery with less residual neurologic involvement. A tryptophan- or phenylalanin-immobilized polyvinyl alcohol gel column (IM-TR 350 or IM-PH 350) semiselectively adsorbs such autoantibodies as rheumatoid factor, anti-DNA antibody, or anti-acetylcholine receptor antibody. A batchwise adsorption test showed that an IM-TR gel adsorbed a larger amount of the IgG anti-GQ1b antibody than did an IM-PH column. Several patients with Fisher's syndrome therefore were given immunoadsorbent therapy using the IM-TR column without adverse reactions. An ex vivo plasma perfusion study done with the IM-TR column confirmed that it effectively adsorbs the IgG anti-GQ1b antibody. Results of adsorption tests done with various amino acid-immobilized gels suggest that both the hydrophobic force of the side chain and the anionic charge of the carboxylic acid in tryptophan are important in the adsorption of the autoantibody by the IM-TR gel. Immunoadsorption using the IM-TR column, which does not need replacement fluids, offers an alternative type of plasmapheresis for Fisher's syndrome.

Topics: Adolescent; Adult; Aged; Ataxia; Autoantibodies; Autoimmune Diseases; Child; Chromatography, Affinity; Enzyme-Linked Immunosorbent Assay; Female; Gangliosides; Humans; Immunoglobulin G; Immunosorbent Techniques; Male; Middle Aged; Nervous System Diseases; Ophthalmoplegia; Plasmapheresis; Polyradiculoneuropathy; Polyvinyl Alcohol; Syndrome; Tryptophan

Anti-GQ1b antibody seems to be a pathogenetic factor in the development of Fisher syndrome (FS). Although several patients received immunoadsorption therapy (IAT), whether it can remove the autoantibody has not yet been clarified. We treated two patients with FS by IAT using tryptophane column (TR-C) and phenylalanine column (PH-C) (TR-C; 9 times altogether in 2 patients, PH-C: twice altogether in 2 patients), and compared the removal ability of IgG anti-GQ1b antibody and immunoglobulin between TR-C and PH-C. TR-C removed the IgG anti-GQ1b antibodies, IgG, IgA and IgM more than PH-C did. TR-C removed the IgG anti-GQ1b antibody more selectively than non-specific immunoglobulin. In practicing IAT on FS, the use of TR-C rather than PH-C is recommended in view of the removal ability of the autoantibody.

Topics: Adult; Autoantibodies; Cerebellar Ataxia; Female; Gangliosides; Humans; Immunoglobulin G; Immunosorbent Techniques; Ophthalmoplegia; Phenylalanine; Polyradiculoneuropathy; Reflex, Abnormal; Syndrome; Tryptophan

Three patients who had diarrhea prior to the development of Miller Fisher syndrome are presented. Campylobacter jejuni was isolated from stool specimens from all patients. High titers of anti-GQ1b IgG antibodies were demonstrated in the serum of these patients by enzyme-linked immunosorbent assay and thin-layer chromatography overlay. In enzyme-linked immunosorbent assay inhibition studies the anti-GQ1b IgG antibodies bound specifically to whole bacteria of the Miller Fisher syndrome-associated C. jejuni strains. The presence of anti-GQ1b IgG binding epitopes on the surface of the C. jejuni from the patients was not exclusively associated with a specific Penner serotype. It is suggested that anti-GQ1b antibodies are formed during the initial infection that elicits Miller Fisher syndrome. The cross-reactivity of anti-GQ1b IgG antibodies with surface epitopes on Miller Fisher syndrome-associated C. jejuni strains supports the hypothesis of molecular mimicry between bacteria and neural tissue.

Topics: Adult; Ataxia; Campylobacter Infections; Campylobacter jejuni; Diarrhea; Epitopes; Gangliosides; Humans; Immunoglobulin G; Male; Molecular Mimicry; Ophthalmoplegia; Syndrome

Topics: Autoantibodies; Chickenpox; Child; Gangliosides; Humans; Male; Oculomotor Nerve Diseases; Syndrome

We isolated Campylobacter jejuni from 2 patients with Fisher's syndrome subsequent to enteritis. Crude lipopolysaccharide fractions were extracted from the bacteria and separated by thin-layer chromatography. Monoclonal antibodies to GQ1b ganglioside (GMR13 and 7F5) reacted with both lipopolysaccharide fractions, indicating that the lipopolysaccharides bear the GQ1b epitope. This is the first report of molecular mimicry between neural tissue components and the antecedent infectious agents of Fisher's syndrome.

Topics: Antibodies, Monoclonal; Campylobacter Infections; Campylobacter jejuni; Cerebellar Ataxia; Chromatography, Thin Layer; Epitopes; Gangliosides; Humans; Lipopolysaccharides; Male; Molecular Mimicry; Ophthalmoplegia; Syndrome

Topics: Aged; Ataxia; Autoantibodies; Bulbar Palsy, Progressive; Gangliosides; Humans; Male; Ophthalmoplegia; Polyradiculoneuropathy; Syndrome

A 15-year-old man developed diplopia, ataxic gait and bulbar palsy. Two days after the onset of neurological symptoms, neurological examination revealed external ophthalmoplegia, cerebellar ataxia, and areflexia. Muscle weakness in the areas innervated by cranial nerves and in the four limbs, and glove and stocking type sensory impairment were also observed. On the 13th hospital day, CSF protein was elevated with normal cellularity. Serum IgM anti-GQ1b antibody was increased, which decreased concurrently with the clinical improvement. Recent studies have revealed the frequent presence of serum anti-GQ1b antibody in Fisher's syndrome. Therefore, this patient showed Fisher's syndrome at the beginning, then evolved to Guillain-Barré syndrome associated with anti-GQ1b antibody, which would support close association between Fisher's syndrome and Guillain-Barré syndrome.

Topics: Adolescent; Autoantibodies; Cerebellar Ataxia; Gangliosides; Humans; Immunoglobulin M; Male; Ophthalmoplegia; Polyradiculoneuropathy; Syndrome

Circulating IgG antibodies to carbohydrate determinants on GQ1b ganglioside are found in the acute phase sera of patients with Miller Fisher syndrome, a variant of Guillain-Barré syndrome. Here we report that the IgG subclass distribution of the anti-GQ1b antibodies is mainly restricted to IgG1 and IgG3 antibodies, subclasses typically associated with a T cell-dependent immune response to protein antigens. This is highly unusual in that IgG responses to carbohydrate determinants are typically of the IgG2 subclass. Anti-GQ1b antibodies also have a limited ability to bind GQ1b in a membrane-like environment, particularly at body temperature. These data suggest that the antigen initiating the immune response in MFS is not likely GQ1b but an unidentified cross-reactive glycoprotein antigen(s). Similar results were obtained for anti-GM1 IgG antibodies in Guillain-Barré syndrome.

Topics: Antibodies; Antibody Formation; Ataxia; Body Temperature; Drug Carriers; Gangliosides; Glycolipids; Humans; Immunoglobulin G; Immunoglobulins; Liposomes; Nerve Growth Factors; Oligoclonal Bands; Ophthalmoplegia; Reflex, Abnormal; Syndrome

Topics: Animals; Autoantibodies; Cells, Cultured; Cerebellar Ataxia; Ganglia, Spinal; Gangliosides; Humans; Neurites; Neurons; Neurotoxins; Ophthalmoplegia; Plasmapheresis; Rats; Rats, Wistar; Reflex, Abnormal; Syndrome

To determine the significance of serum anti-GQ1b IgG antibody, we studied the disease spectrum associated with this antibody and GQ1b epitope in the human nervous system. We examined sera from 19 patients with typical Miller Fisher syndrome (MFS), five patients with acute postinfectious ophthalmoplegia without ataxia (atypical MFS), six patients with Guillain-Barré syndrome (GBS) with ophthalmoplegia (GBS-OP[+]), and 23 patients with GBS without ophthalmoplegia (GBS-OP[-]). We also examined sera from 84 patients with other neurologic or non-neurologic disorders and from 16 normal control subjects. Eighteen of the 19 patients with typical MFS, all the patients with atypical MFS, and five of the six patients with GBS-OP(+) had increased anti-GQ1b IgG activity in ELISA, but none of the patients in the other groups, including GBS-OP(-), had it. All the patients' sera that had anti-GQ1b IgG antibody showed anti-GT1a IgG activity. Results of absorption studies suggested that the same antibody reacted with GQ1b and GT1a. An anti-GQ1b mouse monoclonal antibody immunostained the paranodal regions of the extramedullary portion of the human oculomotor, trochlear, and abducens nerves. Biochemical analysis showed that the human oculomotor nerve contained a larger amount of GQ1b than did the ventral and dorsal roots of the spinal cord. We conclude that serum IgG antibody against GQ1b is very closely associated with acute postinfectious ophthalmoplegia in MFS and GBS.

Topics: Ataxia; Brain Stem; Carbohydrate Conformation; Carbohydrate Sequence; Cerebellum; Chromatography, Thin Layer; Cranial Nerves; Enzyme-Linked Immunosorbent Assay; Gangliosides; Humans; Immunoglobulin G; Immunohistochemistry; Molecular Sequence Data; Nervous System; Ophthalmoplegia; Peripheral Nerves; Polyradiculoneuropathy; Reflex; Spinal Nerve Roots; Syndrome

We studied serum anti-glycolipid antibodies by enzyme-linked immunosorbent assay and thin-layer chromatography-enzyme immunoassay in six consecutive patients with typical Miller Fisher syndrome. In all six, increased activity of IgG antibody against ganglioside GQ1b was present in the early phase and reduced with time, whereas such activity was not detected in normal control subjects and disease control subjects including those with Guillain-Barré syndrome. Anti-GQ1b IgG antibody is a new possible diagnostic marker of Miller Fisher syndrome and could well be related to the disease process itself.

Topics: Adult; Aged; Antibody Specificity; Ataxia; Autoantibodies; Autoimmune Diseases; Biomarkers; Female; Gangliosides; Glycolipids; Humans; Immunoglobulin G; Male; Middle Aged; Multiple Sclerosis; Ophthalmoplegia; Polyradiculoneuropathy; Reflex, Abnormal; Syndrome