g(m1)-ganglioside and Amyotrophic-Lateral-Sclerosis

Topics: Aged; Amyotrophic Lateral Sclerosis; Antibody Specificity; Autoantibodies; Disease Progression; Female; G(M1) Ganglioside; Humans; Immunoglobulin M; Male; Middle Aged; Retrospective Studies

Topics: Amyotrophic Lateral Sclerosis; Autoantibodies; Autoimmune Diseases; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Humans; Immunoglobulin M; Motor Neuron Disease; Sensitivity and Specificity

Pure motor neuropathy syndromes resemble amyotrophic lateral sclerosis variants with no upper motor neuron signs. Their identification is important, as, in contrast to amyotrophic lateral sclerosis, they are often immune mediated and treatable. Typically the immune-mediated motor neuropathy syndromes are distal and asymmetrical and progress slowly. The clinical features may help alert the clinician to the diagnosis, but other ancillary evidence such as abnormalities on electrophysiological testing and the presence of serum autoantibodies to neural antigens are helpful in making the diagnosis more secure. Electrophysiological abnormalities include not only motor conduction block but also other evidence of a demyelinative process such as prolonged distal latencies or F-wave abnormalities. High-titer anti-GM1 antibodies occur frequently but more specific patterns of reactivity may be especially helpful. Treatment of these motor neuropathy syndromes includes cyclophosphamide, which we use in combination with plasma exchange, and in some patients, human immune globulin. Clinical responses to therapy may occur within the first 2 to 4 months in patients with motor neuropathy syndromes with demyelinative features, but only become obvious 6 months or later after starting treatment in patients with predominantly axonal disorders.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Antibody Specificity; Antigens; Autoantibodies; Autoimmune Diseases; Chronic Disease; Cyclophosphamide; Diagnosis, Differential; Female; G(M1) Ganglioside; Humans; Immunosuppressive Agents; Male; Middle Aged; Neural Conduction; Neuromuscular Diseases

Amyotrophic lateral sclerosis (ALS) is a devastating human neurologic disorder which causes atrophy and weakness of skeletal muscles leading to death. Although pathogenesis of most cases of ALS is not known yet, large number of evidence suggest autoimmune mechanisms through clinical, pathological, and laboratory findings, for example, high frequency of the presence of serum monoclonal gammopathy, association of thyroid diseases, and lymphocytic infiltration of brain and spinal cord tissues of patients. Especially recent findings of IgG antibodies against calcium channels and IgM anti-GM1 antibodies are important to elucidate the pathogenesis of ALS. Although conventional immunotherapy may not be effective, multifocal motor neuropathy (MMN) which simulates ALS should be carefully examined because MMN is a treatable disorder.

Topics: Amyotrophic Lateral Sclerosis; Autoantibodies; Calcium Channels; G(M1) Ganglioside; Humans

High titers of IgM anti-GM1 antibodies are commonly found in the serum of patients with some lower motor neuron disorders and peripheral neuropathies. Enzyme-linked immunosorbent assays (ELISA) are useful for the detection and quantitation of anti-GM1 antibodies. Testing for serum anti-GM1 activity is indicated in the diagnostic evaluation of lower motor neuron syndromes. The presence of high titers of anti-GM1 antibodies mandates careful electrophysiologic testing for the motor conduction block that is found in multifocal motor neuropathy, a treatable disorder. Quantitation of anti-GM1 antibodies may also be a useful guide in the treatment of multifocal motor neuropathy. Further study of antiglycolipid antibodies in motor neuron disorders and peripheral neuropathies may provide clues to the events that stimulate these antibodies and to the pathogenesis of such syndromes.

Topics: Amyotrophic Lateral Sclerosis; Antibody Specificity; Autoantibodies; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Humans; Motor Neuron Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases

Topics: Amyotrophic Lateral Sclerosis; Antibodies; Autoantibodies; Epitopes; G(M1) Ganglioside; Humans; Immunoglobulin A; Incidence; Intermediate Filaments; Motor Neurons; Nerve Tissue Proteins; Neuromuscular Diseases; Paraproteinemias

To determine if response to immunosuppressive treatment in motor neuron syndromes could be predicted on the basis of clinical features, anti-GM1 antibodies, or conduction block.. Prospective, uncontrolled, treatment trial using prednisone for 4 months followed by intravenous cyclophosphamide (3 g/m2) continued orally for 6 months.. All patients were referred to university hospital medical centers.. Sixty-five patients with motor neuron syndromes were treated with prednisone; 11 patients had elevated GM1 antibody titers, and 11 patients had conduction block. Forty-five patients received cyclophosphamide, eight of whom had elevated GM1 antibodies and 10 had conduction block.. One patient responded to prednisone, and five patients responded to cyclophosphamide treatment. Only patients with a lower motor neuron syndrome and conduction block improved with either treatment. Response to treatment did not correlate with GM1 antibodies.. GM1 antibodies did not serve as a marker for improvement in patients with motor neuron syndrome treated with immunosuppressive drugs. Patients with amyotrophic lateral sclerosis failed to improve irrespective of laboratory findings.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Cyclophosphamide; Female; G(M1) Ganglioside; Humans; Immunosuppressive Agents; Male; Middle Aged; Motor Neuron Disease; Neural Conduction; Prednisone; Prospective Studies

Alterations in glycosphingolipid metabolism have been linked to the pathophysiological mechanisms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Accordingly, administration of GM1, a sialic acid-containing glycosphingolipid, is protective against neuronal damage and supports neuronal homeostasis, with these effects mediated by its bioactive component, the oligosaccharide head (GM1-OS). Here, we add new evidence to the therapeutic efficacy of GM1 in ALS: Its administration to WT and SOD1

Topics: Amyotrophic Lateral Sclerosis; G(M1) Ganglioside; Glutamic Acid; Humans; Motor Neurons; Neurodegenerative Diseases; Superoxide Dismutase

Multifocal motor neuropathy (MMN) and progressive muscular atrophy (PMA) are associated with IgM monoclonal gammopathy or the presence IgM anti-GM1-antibodies. To further investigate the pathophysiology of MMN and PMA we determined concentrations of 16 mainly B-cell associated inflammatory markers in serum from 25 patients with MMN, 55 patients with PMA, 25 patients with amyotrophic lateral sclerosis (ALS) and 50 healthy controls. Median serum concentrations of the 16 tested cytokines and chemokines were not significantly increased in patients with MMN or patients with PMA, irrespective of the presence of IgM monoclonal gammopathy or high IgM anti-GM1 antibodies. These results argue against a systemic B-cell mediated immune response underlying the pathogenesis of MMN and PMA.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Autoantibodies; B-Cell Activating Factor; Chi-Square Distribution; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Immunoglobulin M; Male; Middle Aged; Muscular Atrophy, Spinal; Polyneuropathies; Statistics, Nonparametric

A patient, who developed an amyotrophic lateral sclerosis-like disorder subsequent to ganglioside treatment, had IgM antibodies to GM2 as well as to minor gangliosides X1 and X2 containing GM2 epitope. These gangliosides as well as GM1 were tested in 655 sera obtained from patients who were suspected of having amyotrophic lateral sclerosis or motor neuron disease to find a treatable condition. Three patients had high titers of IgG anti-GM1 antibodies, but no IgM anti-GM1 antibodies. One of the patients also had IgG anti-X2 antibodies. The patients, being diagnosed with having lower motor neuron syndrome, had neither upper motor neuron signs nor multifocal conduction block. Both IgM and IgG anti-GM1 antibodies should be tested in patients who have lower motor neuron syndrome.

Topics: Amyotrophic Lateral Sclerosis; Complement C3; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Immunoglobulin G; Immunoglobulin M; Male; Retrospective Studies

Lower motor neuron syndromes (LMNS) are heterogenous conditions, which include patients with progressive lower motor neuron disease (LMND) and cases with the clinical phenotype of motor neuropathy (MN). The aim of this study was to estimate the IgM anti-GM1 ganglioside antibodies titer and the ratio of the light chains in order to define the presence of autoimmunity process in particular cases with LMNS. Twenty-eight patients were diagnosed with LMND and 15 patients were diagnosed with MN (10 patients with multifocal motor neuropathy with conduction block, five patients with MN without conduction block). Total of 103 patients with classical amyotrophic lateral sclerosis (ALS) and 50 healthy, age-matched persons were also tested. The IgM anti-GM1 ganglioside titer and the ratio of lambda/kappa light chains in serum were determined using the ELISA technique. High titer of IgM anti-GM1 antibodies were detected in serum of 46% LMND patients, 80% of MN patients, and 18% of the classical ALS cases. An elevated ratio of lambda/kappa light chains appeared in 18% of LMND patients, and in 67% of the MN cases. The lambda/kappa light chains ratio was normal in all ALS patients. The presence of elevated titer of IgM anti-GM1 ganglioside antibodies and the changed ratio of the light chains supports the presence of autoimmune process in LMNS and may provide clues for their management.

Topics: Adult; Amyotrophic Lateral Sclerosis; Autoantibodies; Autoimmunity; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunoglobulin M; Male; Middle Aged; Motor Neuron Disease; Neuromuscular Diseases

We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies, since such antibodies have been associated with PPS and motor neuron disorders. Sera from 144 patients with previous poliomyelitis (105 paralytic, 22 nonparalytic and 17 PPS), 60 with previous Guillain-Barré syndrome, 44 with amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed with ELISA for GM1 IgM, IgG and IgA antibodies. GM1 antibodies were present in 14% of the PPS patients, but the prevalence did not differ significantly from that of the other groups. Our study does not support the hypothesis that GM1 antibodies are involved in the pathogenesis of PPS.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Autoantibodies; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Motor Neurons; Peripheral Nerves; Poliomyelitis; Postpoliomyelitis Syndrome

It has been reported recently that Haemophilus influenzae can elicit an axonal form of Guillain-Barré syndrome. To investigate the incidence and features of H. influenzae-related Guillain-Barré syndrome, anti-H. influenzae antibody titres were measured by enzyme-linked immunosorbent assay (ELISA) in 46 consecutive Japanese patients with Guillain-Barré syndrome, 49 normal controls, 24 patients with multiple sclerosis and 27 patients with amyotrophic lateral sclerosis (ALS). Whole bacteria of non-encapsulated (non-typable) H. influenzae isolated from one of the Guillain-Barré syndrome patients was the antigen used. Elevated anti-H. influenzae antibodies for two or three classes of IgG, IgM and IgA were found in six (13%) Guillain-Barré syndrome patients, but not in the normal controls and patients with multiple sclerosis or ALS. The incidence was significantly higher in patients with Guillain-Barré syndrome than in the normal controls (P = 0.01) and patients with multiple sclerosis or ALS (P = 0.009). Western blot analysis confirmed that the H. influenzae-positive patients' IgG recognized the lipopolysaccharides of H. influenzae. Guillain-Barré syndrome patients with anti-H. influenzae antibodies showed relatively uniform clinical and laboratory features: prodromal respiratory infection, less frequent cranial and sensory nerve involvement, pure motor axonal degeneration on electrophysiology, and positivity for IgG anti-GM1 antibodies. Although the features were similar to those in Guillain-Barré syndrome patients infected by Campylobacter jejuni, the recoveries seemed to be better in patients with H. influenzae-related Guillain-Barré syndrome. It is concluded that a form of Guillain-Barré syndrome occurs after respiratory infection by H. influenzae in the Japanese population. A particular strain of non-typable H. influenzae has a ganglioside GM1-like structure and elicits axonal Guillain-Barré syndrome similar to C. jejuni-related Guillain-Barré syndrome.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Antibodies, Bacterial; Autoantibodies; Axons; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Haemophilus Infections; Haemophilus influenzae; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Multiple Sclerosis; Retrospective Studies

Immunological abnormality is often found in amyotrophic lateral sclerosis (ALS). Antibodies to sulfoglucuronyl paragloboside (SGPG) were reported in ALS, although the pathogenetic significance of the antibodies is still unknown. We have already demonstrated that SGPG, a unique glycolipid, is present in both peripheral nerve and vascular endothelial cells. To investigate whether serum anti-SGPG antibodies would participate in activation and/or injury of endothelial cells in ALS, we examined serum anti-SGPG antibodies in association with serum soluble E- and P-selectins, which are markers of activated endothelial cells, in 25 patients with ALS and 14 age-matched patients with other neurological diseases (ONDs) using the microtiter-ELISA method. Seven out of 25 ALS patients had anti-SGPG antibodies. Levels of sE-selectin were significantly higher in patients with ALS (48.5 +/- 23.4 ng/ml) compared with ONDs (24.0 +/- 11.8 ng/ml) (P < 0.005). Four out of seven ALS patients with anti-SGPG antibodies had concomitantly high sE-selectin levels. The mean sE-selectin levels were higher in patients with anti-SGPG antibodies (61.9 +/- 25.2 ng/ml) than in those without anti-SGPG antibodies (43.3 +/- 21.1 ng/ml). Anti-SGPG antibodies may take part in the activation and/or injury of endothelial cells. The increased expression of E-selectin may be related to an immunological process in some ALS patients.

Topics: Aged; Amyotrophic Lateral Sclerosis; Antibodies; Blood-Brain Barrier; E-Selectin; Female; G(M1) Ganglioside; Globosides; Humans; Male; Middle Aged; P-Selectin

Highly elevated titers of serum anti-GM1 ganglioside antibodies are closely associated with multifocal motor neuropathy, but low titers are commonly present in normal individuals or other diseases. Current systems for measuring anti-GM1 antibodies utilize the enzyme-linked immunosorbent assay (ELISA), in which serum dilutions are tested for binding to excess antigen immobilized on the surface of microwells. The ELISA system, however, is relatively time consuming, labor intensive, and costly, in addition to being prone to methodological variability. We have developed a novel agglutination assay for the detection of anti-GM1 antibodies, utilizing GM1 ganglioside-coated latex beads. In contrast to the ELISA system, antibody titers may be quantified by testing for agglutination using latex beads coated with decreasing amounts of antigen. The agglutination assay compares favorably to the ELISA system in sensitivity and specificity, but is considerably less costly and takes only a few minutes to perform.

Topics: Amyotrophic Lateral Sclerosis; Antibodies; Demyelinating Diseases; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Humans; Latex Fixation Tests; Miller Fisher Syndrome; Nervous System Diseases; Reproducibility of Results; Sensitivity and Specificity

Electrodiagnostic testings including electromyography have become increasingly important tools in clinical practice of neurology. These tests should not merely be referred to a technician, but be viewed as a clinical tool used by a neurologist. Recent advances in clinical electromyography, nerve conduction tests, and tests for axonal function including the newly developed threshold electrotonus are reviewed. These not only serve as a diagnostic tool, but also are useful in clinical trials by providing an objective parameter of nerve function. Computerized threshold tracking techniques such as threshold electrotonus enable us to monitor molecular events in various ion channels in axons of patients. Further development is expected toward clinical molecular neurophysiology.

Topics: Amyotrophic Lateral Sclerosis; Autoantibodies; Axons; Diagnosis, Differential; Electrodiagnosis; Electromyography; Electrophysiology; Excitatory Postsynaptic Potentials; G(M1) Ganglioside; Humans; Motor Neuron Disease; Neural Conduction

An autoimmune basis has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). This hypothesis is supported by the presence of antibodies that interact with motoneuron antigens in serum of these patients. Against autoimmunity are the discrepances in the frequency of the antibodies appearance and also failure of immunosuppression. The aim of our study was to evaluate the titer of antibodies against GM1-gangliosides, AGM1-gangliosides and anti-sulfatides in paired serum and cerebrospinal fluid samples in the ALS patients.. Serum of 103 and CSF of 79 patients with ALS was examined. The "disease controls" consisted of 22 cases of other motor neuron diseases and 50 healthy, age-matched normals. CSF was drawn at the same time from 79 ALS patients, 6 cases of the "disease controls" and 50 normals. To study the titer of antibodies against GM1-gangliosides, AGM1-gangliosides and sulfatides the ELISA technique has been applied.. An increased titer against GM1-gangliosides, AGM1-gangliosides and sulfatides in ALS appeared in serum in 18%, 32%, and 11%, resp., in the "disease controls" the increased antibodies titer appeared in single cases. In CSF the appropriate values in ALS were 20%, 15%, 8%, resp. In the "disease controls" a high antibodies titer was a rare finding.. It is concluded that in some ALS cases and also in some patients with other motor neuron diseases an autoimmune mechanism may contribute to motor neuron injury.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Autoantibodies; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Motor Neurons

IgM anti-GM1 antibodies occur with increased frequency in the serum of patients with multifocal motor neuropathy (MMN). We tested the ability of serum IgM from patients with MMN to bind to GM1 ganglioside covalently bound to secondary amino groups on ELISA plates (Co-GM1). The Co-GM1 technique detected high titer (> 1,800), selective, serum IgM binding to GM1 ganglioside in 85% of our MMN patients (23/27), a significantly greater frequency compared with figures of 37% and 52% found using our previous testing methods. Selective IgM anti-GM1 antibodies showed disease specificity. The only other patients with selective, high-titer IgM anti-GM1 antibodies had either chronic motor neuropathy without conduction block or acute immune neuropathy in China. No patient from the amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré, or systemic immune disorder control groups had selective IgM anti-GM1 antibodies at titers greater than 1,800 detected using Co-GM1 ganglioside as ELISA antigen. Titers of IgM anti-GM1 antibodies in MMN (averaging 31,000 +/- 15,000) were more than fourfold higher with Co-GM1 than with previous anti-GM1 assay methods, using conventional ELISA plates with GM-1 antigen alone (7,200 +/- 4,400) or in a lipid environment (3,600 +/- 1,300). We conclude that using ELISA testing with Co-GM1 antigen, serum anti-GM1 autoantibodies are a useful marker for MMN, because they are present in 85% of MMN patients and, at titers greater than 1,800, have strong specificity for immune-mediated motor neuropathies.

Topics: Amyotrophic Lateral Sclerosis; Antigen-Antibody Reactions; Autoantibodies; Demyelinating Diseases; Diagnostic Techniques, Neurological; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Humans; Immunoglobulin M; Motor Neuron Disease; Sensitivity and Specificity

Elevated titers of antibodies directed at ganglioside epitopes have been associated with multifocal motor neuropathy (MMN), motor variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), amyolrophic lateral sclerosis (ALS), and other motor neuropathies. Anti-GM1 antibodies were measured in 675 patients: 180 age- and sex-stratified healthy blood bank controls, 132 normal controls who had full neurologic assessment including electromyography, 121 patients with definite ALS, 19 patients with pure sensory neuropathy, and 173 consecutive patient serum samples submitted for GM1 antibody testing. Antibodies to three ganglioside epitopes were determined by ELISA: IgM and IgG anti-monosialo GM1, asialo GM1, and disialo GD1b. Antibody titers for normal subjects and patients with ALS were used to determine normal values and borderline levels below which 99% of normal and 99% of ALS patient titers were found. Clinical evaluation of the next 173 consecutive patients referred for anti-GM1 antibody testing revealed 36 patients with motor neuropathies. Sera from 18 of these patients had titers above the 99% normal threshold and 14 had titers above the ALS and normal borderline threshold. All 14 with elevated sera titers were from patients with motor neuropathy or neuronopathy. Sixteen patients met the clinical and electrophysiologic criteria for MMN; 10 had elevated titers. Ten patients had the motor variant of CIDP without conduction block and three had elevated titers. Anti-IgM asialo GM1 antibodies had the highest sensitivity and specificity. High-titer IgM antibodies against monosialo GM1 occurred only in patients with various forms of pure motor neuropathy (100% specificity). The sensitivity was 50% for this referral-based population.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Antibodies; Epitopes; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Motor Neuron Disease; Sensitivity and Specificity

The significance of the association of motor neuron syndromes with anti-GM1 antibodies remains unclear. We report the immunological study of a juvenile case of amyotrophic lateral sclerosis (ALS).. Serum anti-Gm1 and anti-neurofilament antibodies were assayed by ELISA and western blotting and cerebrospinal fluid (CSF) isoelectrofocusing was performed. Immunocytochemical studies were carried out with the patient's serum and CSF on human brain and spinal cord sections.. Serum polyclonal IgM anti-GM1, anti-neurofilament antibodies and CSF oligoclonal bands were detected. Furthermore, an in vitro production of anti-GM1 IgM was demonstrated. Immunocytochemical studies showed cytoplasm motor neuron immunostaining, due to both IgG and IgM, that substantially decreased after immunoabsorption of the serum with bovine neurofilament proteins but not with GM1-containing liposomes. No immunostaining was obtained with CSF. Immunosuppressive treatment with cyclophosphamide and two cycles of plasma exchanges lowered anti-GM1 antibody levels, but did not determine any clinical improvement.. To our knowledge, this is the first report of ALS, associated with circulating levels and in vitro production of polyclonal IgM anti-GM1, anti-neurofilament antibodies and CSF oligoclonal bands. These findings suggest the occurrence in our patients of an autoimmune process that could be involved in the pathogenesis of ALS.

Topics: Adult; Amyotrophic Lateral Sclerosis; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Brain Chemistry; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Fatal Outcome; G(M1) Ganglioside; Humans; Immunoglobulin M; Immunohistochemistry; In Vitro Techniques; Magnetic Resonance Imaging; Male; Spinal Cord

Six of 110 patients (5.5%) with forms of motor neuron disease had abnormal titers of GM1 antibodies of 1:1,600 or higher. Four others came with previously known high titers. Three patients with upper motor neuron (UMN) signs had titers of 1,600; those with probable or no UMN signs had higher titers. Nine patients had conduction block; six of them had abnormal antibody titers, four with 6,400 or higher. Therefore, patients with motor neuron disease and abnormal anti-GM1 titers may have UMN signs or conduction block.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Autoantibodies; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Motor Neuron Disease; Paraproteinemias

Topics: Amyotrophic Lateral Sclerosis; Antibodies; G(M1) Ganglioside; Humans; Physical Examination; Rabies Vaccines

We studied the ability of anti-GM1 ganglioside antibodies to bind to GM1 in a lipid, "membrane-like" environment. Liposomes containing GM1 were synthesized to simulate this environment. We then compared the binding of anti-GM1 a autoantibodies to GM-1-liposomes and to purified GM1. Antibody binding was quantitated using enzyme-linked immunosorbent assay methodology. Our results showed a 250-fold variation in the ability of anti-GM1 antibodies to bind to GM1-liposomes. There was no correlation between GM-1-liposome binding and the carbohydrate specificities of the anti-GM1 antibodies. However, anti-GM1 antibodies from patients with amyotrophic lateral sclerosis (ALS) showed a 4 fold greater binding to GM1-liposomes than antibodies from patients with lower motor neuron (LMN) syndromes. We conclude that a lipid, presumably "membrane-like", environment may greatly influence the degree of anti-GM1 antibody binding to GM1. The low levels of anti-GM1 antibody binding to GM1-liposomes in patients with LMN syndromes may provide a diagnostic means for distinguishing these patients from those with ALS. Anti-GM1 antibodies from patients with ALS may bind especially well to neuronal membranes containing GM1 in vivo.

Topics: Amyotrophic Lateral Sclerosis; Autoantibodies; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Humans; Immunoglobulin M; Liposomes; Motor Neuron Disease

Clinical correlations of antiganglioside GM1 antibodies are important because high titers of these antibodies may have therapeutic significance. To further evaluate this significance, we reviewed our experience with 78 patients who had the following diagnoses: amyotrophic lateral sclerosis (ALS), ALS syndromes in patients with gammopathy or thyroid abnormalities, cervical spondylosis simulating ALS, motor neuropathies, and chronic inflammatory demyelinating polyneuropathies (CIDP). Antiganglioside antibody titers were measured "blind" by ELISA assay at the neuromuscular clinical laboratory, Johns Hopkins School of Medicine. We conclude that anti-GM1 antibodies are found in a wide variety of neuromuscular conditions. Patients with classical ALS had a mean anti-GM1 antibody titer significantly lower than patients with CIDP or motor neuropathy. Patients with ALS associated with gammopathy or thyroid disorders had higher anti-GM1 titers than seen in classical ALS. The highest mean titer occurred in patients with CIDP, a treatable neuropathy.

Topics: Amyotrophic Lateral Sclerosis; Autoantibodies; Cervical Vertebrae; Demyelinating Diseases; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Motor Neuron Disease; Spinal Osteophytosis

Patients with motor neuron disease with thyroid disorders have been described, although the relationship between the two conditions is unclear. We treated a patient with amyotrophic lateral sclerosis who also had a follicular adenoma of the thyroid gland. Because thyroid gland plasma membranes contain high concentrations of complex gangliosides, such as GD1b, and some patients with motor neuron disease have IgM antibodies to GD1b, we decided to assay serum from this patient for the presence of antiganglioside antibodies. IgM antibodies to GD1b were detectable at serum dilutions of 1:500 and 1:1000 by enzyme-linked immunosorbent assay. While these titers are less than those usually described in patients with plasma cell dyscrasia, they are well in excess of normal values. Antibody to GM1 was also detectable at a lower (1:100) dilution. We do not know the importance of the anti-GD1b antibodies in this patient, but it is possible that antibodies to GD1b are involved in this and other cases of motor neuron disease associated with thyroid disease.

Topics: Adenoma; Amyotrophic Lateral Sclerosis; Antibodies; G(M1) Ganglioside; Gangliosides; Humans; Male; Middle Aged; Thyroid Neoplasms

The incidence of anti-GM1 antibodies in the serum of 104 patients with neurological diseases, 35 patients with non-neurological diseases (NND) and 41 normal controls was determined by enzyme-linked immunosorbent assay (ELISA). Anti-GM1 antibodies were found in 90% of patients presenting with a motor neuropathy (all except one had multifocal conduction blocks). A large proportion (60%) of these patients displayed high antibody titer ranging from 101 to 788. A low incidence of anti-GM1 antibodies was found in the other groups of patients, i.e. 21% of amyotrophic lateral sclerosis (ALS), 26% of other neurological diseases (OND) and 23% of NND. High antibody titers ranging from 106 to 260 were found in two (5%) ALS patients, one (2%) OND patient (myasthenia gravis), and one (3%) NND patient (Waldenström's disease). This study shows that high titers of anti-GM1 antibodies are found in a large proportion of patients with motor neuropathy with multifocal conduction blocks. This argues for a possible autoimmune origin of this neuropathy. We suggest that anti-GM1 antibody determination should be included systematically in the evaluation of all patients with motor neuron diseases and predominantly motor neuropathies.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Antibodies; G(M1) Ganglioside; Humans; Immunoglobulin G; Immunoglobulin M; Middle Aged; Neuromuscular Diseases

Recent studies reported the presence of anti-ganglioside antibodies in occasional patients with motor neuron disease. We found polyclonal serum IgM anti-GM1 antibodies by an anti-GM1 enzyme-linked immunosorbent assay (ELISA) in 9 (19%) of 48 patients with motor neuron disease. A comparable frequency of IgM anti-GM1 antibodies was found in 4 (10%) of 40 sera from patients with other neurological disease. Three (17%) of 18 sera from the patients with motor neuron disease and 2 (17%) of 12 sera from patients with other neurological diseases had anti-GM1 immunostaining as shown by thin layer chromatography immunoblot. One patient with a lower motor neuron variant of motor neuron disease or motor axonopathy without multifocal conduction block had a markedly elevated polyclonal IgM anti-GM1 ELISA titer (greater than 1:64,000) with prominent immunostaining of GM1, moderate immunostaining of GM2, and weak and inconsistent immunostaining of GD1b by thin layer chromatography immunoblot. Treatment with prednisone resulted in clinical improvement despite increasing anti-GM1 antibody titers. These data indicate that patients with motor neuron disease have measurable levels of anti-ganglioside antibodies as frequently as patients with other neurological diseases. This contrasts with a small subgroup of patients with a lower motor neuron variant of motor neuron disease or motor axonopathy who have markedly elevated levels of serum anti-ganglioside antibodies and a clinical syndrome that is treatable with immunosuppression.

Topics: Amyotrophic Lateral Sclerosis; Autoantibodies; Female; G(M1) Ganglioside; Humans; Immunoglobulin mu-Chains; Middle Aged; Motor Neurons; Neuromuscular Diseases

We studied a patient with amyotrophic lateral sclerosis, multifocal motor conduction block, and IgM anti-GM1 antibodies. A sural nerve biopsy demonstrated deposits of IgM at nodes of Ranvier by direct immunofluorescence. The deposits were granular and located in the nodal gap between adjacent myelin internodes, and in some instances, they extended along the surface of the paranodal myelin sheath. When injected into rat sciatic nerve, the serum IgM bound to the nodes of Ranvier, and the binding activity was removed by preincubation with GM1. These observations suggest that anti-GM1 antibodies may have caused motor dysfunction by binding to the nodal and paranodal regions of peripheral nerve.

Topics: Adult; Amyotrophic Lateral Sclerosis; Antibodies; Blood Physiological Phenomena; Electrodiagnosis; Female; Fluorescent Antibody Technique; G(M1) Ganglioside; Humans; Immunoglobulin M; Motor Neurons; Nerve Fibers; Neural Conduction; Neuromuscular Diseases; Ranvier's Nodes; Sciatic Nerve

Topics: Amyotrophic Lateral Sclerosis; Antibody Specificity; Blood Group Antigens; Cross Reactions; G(M1) Ganglioside; Humans

We studied the incidence and clinical correlates of serum antibodies to GM1 and GD1a gangliosides in patients with classical amyotrophic lateral sclerosis (ALS) and other "motor nerve" syndromes. Serum antibodies to GM1 and GD1a gangliosides were measured using enzyme-linked immunosorbent assays. Our results showed that polyclonal immunoglobulin M (IgM) antibodies to the GM1 or GD1a ganglioside or both were present at serum dilutions of 1:25 to 1:4,000 in 78% (57/73) of patients with ALS. Only 8% of normal controls had similar antibodies. The pattern of serum antibody reactivity correlated with the pattern of clinical involvement in our patients. Selective reactivity to GD1a ganglioside was common when upper motor neuron signs were prominent. IgM reactivity to GM1 ganglioside was common in ALS patients with prominent lower motor neuron signs. Most patients with motor neuropathies had serum reactivity to both GM1 and GD1a gangliosides. These results provide further evidence of ongoing autoimmune processes in ALS patients. There is a strong relationship between serum antiganglioside antibodies and patterns of clinical involvement in ALS.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Antibodies; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Middle Aged

We report the presence of serum antibodies directed against GM1 ganglioside, a defined neural antigen, in many patients with amyotrophic lateral sclerosis (ALS). We examined serum from a series of patients with well-documented clinical diagnoses. Serum antibodies to GM1 ganglioside were measured using ELISA assays. Our results showed that polyclonal IgM anti-GM1 antibodies were present at dilutions of 1:25 to 1:2,000 in 42 of 74 (57%) patients with ALS. The anti-GM1 antibodies were especially frequent in patients with prominent lower motor neuron signs (41/59; 69%). Few normal controls (2/23) and motor-sensory neuropathy patients (3/27) had similar antibodies. Anti-GM1 antibodies did occur in patients with nonneural autoimmune disorders. However, the anti-GM1 antibodies in these patients tended to differ from those in ALS based on an analysis of their light chain types. Further examination of the role and spectrum of serum antiganglioside antibody activity in motor neuron syndromes is warranted.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Antibodies; G(M1) Ganglioside; Humans; Immunoglobulin M; Middle Aged

Topics: Amyotrophic Lateral Sclerosis; Animals; Brain; Brain Chemistry; Epilepsy; Female; G(M1) Ganglioside; Gangliosides; Humans; Memory; Mice; Pregnancy; Prenatal Exposure Delayed Effects; Tissue Distribution